Silicone hydrogel lens with a crosslinked hydrophilic coating

ABSTRACT

The invention is related to a cost-effective method for making a silicone hydrogel contact lens having a crosslinked hydrophilic coating thereon. A method of the invention involves heating a silicone hydrogel contact lens in an aqueous solution in the presence of a water-soluble, highly branched, thermally-crosslinkable hydrophilic polymeric material having positively-charged azetidinium groups, to and at a temperature from about 40° C. to about 140° C. for a period of time sufficient to covalently attach the thermally-crosslinkable hydrophilic polymeric material onto the surface of the silicone hydrogel contact lens through covalent linkages each formed between one azetidinium group and one of the reactive functional groups on and/or near the surface of the silicone hydrogel contact lens, thereby forming a crosslinked hydrophilic coating on the silicone hydrogel contact lens. Such method can be advantageously implemented directly in a sealed lens package during autoclave.

This application claims the benefit under 35 USC §119 (e) of U.S.provisional application Nos. 61/369,102 filed 30 Jul. 2010 and61/448,478 filed 2 Mar. 2011, incorporated by reference in theirentireties.

The present invention generally relates to a cost-effective andtime-efficient method for applying a crosslinked hydrophilic coatingonto a silicone hydrogel contact lens to improve its hydrophilicity andlubricity. In addition, the present invention provides an ophthalmiclens product.

BACKGROUND

Soft silicone hydrogel contact lenses are increasingly becoming popularbecause of their high oxygen permeability and comfort. But, a siliconehydrogel material typically has a surface, or at least some areas of itssurface, which is hydrophobic (non-wettable) and susceptible toadsorbing lipids or proteins from the ocular environment and may adhereto the eye. Thus, a silicone hydrogel contact lens will generallyrequire a surface modification.

A known approach for modifying the hydrophilicity of a relativelyhydrophobic contact lens material is through the use of a plasmatreatment, for example, commercial lenses such as Focus NIGHT & DAY™ andO2OPTIX™ (CIBA VISION), and PUREVISION™ (Bausch & Lomb) utilize thisapproach in their production processes. Advantages of a plasma coating,such as, e.g., those may be found with Focus NIGHT & DAY™, are itsdurability, relatively high hydrophilicity/wettability), and lowsusceptibility to lipid and protein deposition and adsorption. But,plasma treatment of silicone hydrogel contact lenses may not be costeffective, because the preformed contact lenses must typically be driedbefore plasma treatment and because of relative high capital investmentassociated with plasma treatment equipment.

Another approach for modifying the surface hydrophilicity of a siliconehydrogel contact lens is the incorporation of wetting agents(hydrophilic polymers) into a lens formulation for making the siliconehydrogel contact lens as proposed in U.S. Pat. Nos. 6,367,929,6,822,016, 7,052,131, and 7,249,848. This method may not requireadditional posterior processes for modifying the surface hydrophilicityof the lens after cast-molding of silicone hydrogel contact lenses.However, wetting agents may not be compatible with the siliconecomponents in the lens formulation and the incompatibility may imparthaziness to the resultant lenses. Further, such surface treatment may besusceptible to lipid deposition and adsorption. In addition, suchsurface treatment may not provide a durable surface for extended wearpurposes.

A further approach for modifying the hydrophilicity of a relativelyhydrophobic contact lens material is a layer-by-layer (LbL) polyionicmaterial deposition technique (see for example, U.S. Pat. No. 6,451,871,U.S. Pat. No. 6,717,929, U.S. Pat. No. 6,793,973, U.S. Pat. No.6,884,457, U.S. Pat. No. 6,896,926, U.S. Pat. No. 6,926,965, U.S. Pat.No. 6,940,580, and U.S. Pat. No. 7,297,725, and U.S. Patent ApplicationPublication Nos. US 200710229758A1, US 200810174035A1, and US2008/0152800A1). Although the LbL deposition technique can provide acost effective process for rendering a silicone hydrogel materialwettable, LbL coatings may not be as durable as plasma coatings and mayhave relatively high densities of surface charges; which may interferewith contact lens cleaning and disinfecting solutions. To improve thedurability, crosslinking of LbL coatings on contact lenses has beenproposed in commonly-owned copending US patent application publicationNos. 2008/0226922 A1 and 2009/0186229 A1 (incorporated by reference intheir entireties). However, crosslinked LbL coatings may have ahydrophilicity and/or wettability inferior than original LbL coatings(prior to crosslinking) and still have relative high densities ofsurface charges.

A still further approach for modifying the hydrophilicity of arelatively hydrophobic contact lens material is to attach hydrophilicpolymers onto contact lenses according to various mechanisms (see forexample, U.S. Pat. Nos. 6,099,122, 6,436,481, 6,440,571, 6,447,920,6,465,056, 6,521,352, 6,586,038, 6,623,747, 6,730,366, 6,734,321,6,835,410, 6,878,399, 6,923,978, 6,440,571, and 6,500,481, US PatentApplication Publication Nos. 2009/0145086 A1, 2009/0145091A1,2008/0142038A1, and 2007/0122540A1, all of which are herein incorporatedby reference in their entireties). Although those techniques can be usein rendering a silicone hydrogel material wettable, they may not becost-effective and/or time-efficient for implementation in a massproduction environment, because they typically require relatively longtime and/or involve laborious, multiple steps to obtain a hydrophiliccoating.

Therefore, there is still a need for a method of producing siliconehydrogel contact lenses with wettable and durable coating (surface) in acost-effective and time-efficient manner.

SUMMARY OF THE INVENTION

The invention, in one aspect, provides a method for producing siliconehydrogel contact lenses each having a crosslinked hydrophilic coatingthereon, the method of invention comprising the steps of: (a) obtaininga silicone hydrogel contact lens and a water-soluble andthermally-crosslinkable hydrophilic polymeric material, wherein thecontact lens comprises amino and/or carboxyl groups on and/or near thesurface of the contact lens, wherein the hydrophilic polymeric materialcomprises (i) from about 20% to about 95% by weight of first polymerchains derived from an epichlorohydrin-functionalized polyamine orpolyamidoamine, (ii) from about 5% to about 80% by weight of hydrophilicmoieties or second polymer chains derived from at least onehydrophilicity-enhancing agent having at least one reactive functionalgroup selected from the group consisting of amino group, carboxyl group,thiol group, and combination thereof, wherein the hydrophilic moietiesor second polymer chains are covalently attached to the first polymerchains through one or more covalent linkages each formed between oneazetitdinium group of the epichlorohydrin-functionalized polyamine orpolyamidoamine and one amino, carboxyl or thiol group of thehydrophilicity-enhancing agent, and (iii) azetidinium groups which areparts of the first polymer chains or pendant or terminal groupscovalently attached to the first polymer chains; and (b) heating thecontact lens in an aqueous solution in the presence of the hydrophilicpolymeric material to and at a temperature from about 40° C. to about140° C. for a period of time sufficient to covalently attach thehydrophilic polymeric material onto the surface of the contact lensthrough second covalent linkages each formed between one azetidiniumgroup of the hydrophilic polymeric material and one of the amino and/orcarboxyl groups on and/or near the surface of the contact lens, therebyforming a crosslinked hydrophilic coating on the contact lens.

In another aspect, the invention provides a silicone hydrogel contactlens obtained according to a method of the invention, wherein thesilicone hydrogel contact lens has an oxygen permeability of at leastabout 40 barrers, a surface wettability characterized by a water contactangle of about 100 degrees or less, and a good coating durabilitycharacterized by surviving a digital rubbing test.

In a further aspect, the invention provides an ophthalmic product, whichcomprises a sterilized and sealed lens package, wherein the lens packagecomprises: a post-autoclave lens packaging solution and a readily-usablesilicone hydrogel contact lens immersed therein, wherein thereadily-usable silicone hydrogel contact lens comprises a crosslinkedhydrophilic coating obtained by autoclaving an original siliconehydrogel contact lens having amino groups and/or carboxyl groups onand/or near the surface of the original silicone hydrogel contact lensin a pre-autoclave packaging solution containing a water-soluble andthermally-crosslinkable hydrophilic polymeric material, wherein thehydrophilic polymeric material comprises (i) from about 20% to about 95%by weight of first polymer chains derived from anepichlorohydrin-functionalized polyamine or polyamidoamine, (ii) fromabout 5% to about 80% by weight of hydrophilic moieties or secondpolymer chains derived from at least one hydrophilicity-enhancing agenthaving at least one reactive functional group selected from the groupconsisting of amino group, carboxyl group, thiol group, and combinationthereof, wherein the hydrophilic moieties or second polymer chains arecovalently attached to the first polymer chains through one or morecovalent linkages each formed between one azetitdinium group of theepichlorohydrin-functionalized polyamine or polyamidoamine and oneamino, carboxyl or thiol group of the hydrophilicity-enhancing agent,and (iii) azetidinium groups which are parts of the first polymer chainsor pendant or terminal groups covalently attached to the first polymerchains, wherein the hydrophilic polymeric material is covalentlyattached onto the silicone hydrogel contact lens through second covalentlinkages each formed between one amino or carboxyl group on and/or nearthe surface of the silicone hydrogel contact lens and one azetidiniumgroup of the hydrophilic polymeric material, wherein the post-autoclavepackaging solution comprises at least one buffering agent in an amountsufficient to maintain a pH of from about 6.0 to about 8.5 and anhydrolyzed product of the hydrophilic polymeric material and has atonicity of from about 200 to about 450 milliosmol (mOsm) and aviscosity of from about 1 centipoise to about 20 centipoises.

In a still further aspect, the invention provides a water-soluble andthermally-crosslinkable hydrophilic polymeric material, which comprises:(a) from about 20% to about 95% by weight of first polymer chainsderived from an epichlorohydrin-functionalized polyamine orpolyamidoamine; (b) from about 5% to about 80% by weight of secondpolymer chains derived from at least one hydrophilicity-enhancingpolymeric agent having at least one reactive functional group selectedfrom the group consisting of amino group, carboxyl group, thiol group,and combination thereof, wherein the second polymer chains arecovalently attached to the first polymer chains through one or morecovalent linkages each formed between one azetitdinium group of theepichlorohydrin-functionalized polyamine or polyamidoamine and oneamino, carboxyl or thiol group of the hydrophilicity-enhancing polymericagent; and (c) azetidinium groups which are parts of the first polymerchains or pendant or terminal groups covalently attached to the firstpolymer chains.

These and other aspects of the invention will become apparent from thefollowing description of the presently preferred embodiments. Thedetailed description is merely illustrative of the invention and doesnot limit the scope of the invention, which is defined by the appendedclaims and equivalents thereof. As would be obvious to one skilled inthe art, many variations and modifications of the invention may beeffected without departing from the spirit and scope of the novelconcepts of the disclosure.

DETAILED DESCRIPTION OF EMBODIMENTS OF THE INVENTION

Reference now will be made in detail to the embodiments of theinvention. It will be apparent to those skilled in the art that variousmodifications, variations and combinations can be made in the presentinvention without departing from the scope or spirit of the invention.For instance, features illustrated or described as part of oneembodiment, can be used on another embodiment to yield a still furtherembodiment. Thus, it is intended that the present invention cover suchmodifications, variations and combinations as come within the scope ofthe appended claims and their equivalents. Other objects, features andaspects of the present invention are disclosed in or are obvious fromthe following detailed description. It is to be understood by one ofordinary skill in the art that the present discussion is a descriptionof exemplary embodiments only, and is not intended as limiting thebroader aspects of the present invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Generally, the nomenclatureused herein and the laboratory procedures are well known and commonlyemployed in the art. Conventional methods are used for these procedures,such as those provided in the art and various general references. Wherea term is provided in the singular, the inventors also contemplate theplural of that term. The nomenclature used herein and the laboratoryprocedures described below are those well known and commonly employed inthe art.

A “silicone hydrogel contact lens” refers to a contact lens comprising asilicone hydrogel material. A “silicone hydrogel” refers to asilicone-containing polymeric material which can absorb at least 10percent by weight of water when it is fully hydrated and is obtained bycopolymerization of a polymerizable composition comprising at least onesilicone-containing vinylic monomer or at least one silicone-containingvinylic macromer or at least one silicone-containing prepolymer havingethylenically unsaturated groups.

A “vinylic monomer”, as used herein, refers to a compound that has onesole ethylenically unsaturated group and can be polymerized actinicallyor thermally.

The term “olefinically unsaturated group” or “ethylenically unsaturatedgroup” is employed herein in a broad sense and is intended to encompassany groups containing at least one >C═C< group. Exemplary ethylenicallyunsaturated groups include without limitation (meth)acryloyl

allyl, vinyl

styrenyl, or other C═C containing groups.

The term “(meth)acrylamide” refers to methacrylamide and/or acrylamide.

The term “(meth)acrylate” refers to methacrylate and/or acrylate.

A “hydrophilic vinylic monomer”, as used herein, refers to a vinylicmonomer which as a homopolymer typically yields a polymer that iswater-soluble or can absorb at least 10 percent by weight water whenfully hydrated.

A “hydrophobic vinylic monomer”, as used herein, refers to a vinylicmonomer which as a homopolymer typically yields a polymer that isinsoluble in water and can absorb less than 10 percent by weight water.

A “macromer” or “prepolymer” refers to a medium and high molecularweight compound or polymer that contains two or more ethylenicallyunsaturated groups. Medium and high molecular weight typically meansaverage molecular weights greater than 700 Daltons.

A “crosslinker” refers to a compound having at least two ethylenicallyunsaturated groups. A “crosslinking agent” refers to a crosslinkerhaving a molecular weight of about 700 Daltons or less.

A “polymer” means a material formed by polymerizing/crosslinking one ormore monomers or macromers or prepolymers.

“Molecular weight” of a polymeric material (including monomeric ormacromeric materials), as used herein, refers to the weight-averagemolecular weight unless otherwise specifically noted or unless testingconditions indicate otherwise.

The term “amino group” refers to a primary or secondary amino group offormula —NHR′, where R′ is hydrogen or a C₁-C₂₀ unsubstituted orsubstituted, linear or branched alkyl group, unless otherwisespecifically noted.

An “epichlorohydrin-functionalized polyamine” or“epichlorohydrin-functionalized polyamidoamine” refers to a polymerobtained by reacting a polyamine or polyamidoamine with epichlorohydrinto convert all or a substantial percentage of amine groups of thepolyamine or polyamidoamine into azetidinium groups.

An “azetidinium group” refers to a positively charged group of

The term “thermally-crosslinkable” in reference to a polymeric materialor a functional group means that the polymeric material or thefunctional group can undergo a crosslinking (or coupling) reaction withanother material or functional group at a relatively-elevatedtemperature (from about 40° C. to about 140° C.), whereas the polymericmaterial or functional group cannot undergo the same crosslinkingreaction (or coupling reaction) with another material or functionalgroup at room temperature (i.e., from about 22° C. to about 28° C.,preferably from about 24° C. to about 26° C., in particular at about 25°C.) to an extend detectable for a period of about one hour.

The term “phosphorylcholine” refers to a zwitterionic group of in whichn is an integer of 1 to 5 and R₁, R₂ and R₃ independently of each otherare C₁-C₈ alkyl or C₁-C₈ hydroxyalkyl.

The term “reactive vinylic monomer” refers to a vinylic monomer having acarboxyl group or an amino group (i.e., a primary or secondary aminogroup).

The term “non-reactive hydrophilic vinylic monomer” refers to ahydrophilic vinylic monomer which is free of any carboxyl group or aminogroup (i.e., primary or secondary amino group). A non-reactive vinylicmonomer can include a tertiary or quaternary amino group.

The term “water-soluble” in reference to a polymer means that thepolymer can be dissolved in water to an extent sufficient to form anaqueous solution of the polymer having a concentration of up to about30% by weight at room temperature (defined above).

A “water contact angle” refers to an average water contact angle (i.e.,contact angles measured by Sessile Drop method), which is obtained byaveraging measurements of contact angles with at least 3 individualcontact lenses.

The term “intactness” in reference to a coating on a silicone hydrogelcontact lens is intended to describe the extent to which the contactlens can be stained by Sudan Black in a Sudan Black staining testdescribed in Example 1. Good intactness of the coating on a siliconehydrogel contact lens means that there is practically no Sudan Blackstaining of the contact lens.

The term “durability” in reference to a coating on a silicone hydrogelcontact lens is intended to describe that the coating on the siliconehydrogel contact lens can survive a digital rubbing test.

As used herein, “surviving a digital rubbing test” or “surviving adurability test” in reference to a coating on a contact lens means thatafter digitally rubbing the lens according to a procedure described inExample 1, water contact angle on the digitally rubbed lens is stillabout 100 degrees or less, preferably about 90 degrees or less, morepreferably about 80 degrees or less, most preferably about 70 degrees orless.

The intrinsic “oxygen permeability”, Dk, of a material is the rate atwhich oxygen will pass through a material. In accordance with theinvention, the term “oxygen permeability (Dk)” in reference to ahydrogel (silicone or non-silicone) or a contact lens means an oxygenpermeability (Dk) which is corrected for the surface resistance tooxygen flux caused by the boundary layer effect according to theprocedures shown in Examples hereinafter. Oxygen permeability isconventionally expressed in units of barrers, where “barrer” is definedas [(cm³ oxygen)(mm)/(cm²)(sec)(mm Hg)]×10⁻¹⁰.

The “oxygen transmissibility”, Dk/t, of a lens or material is the rateat which oxygen will pass through a specific lens or material with anaverage thickness of t [in units of mm] over the area being measured.Oxygen transmissibility is conventionally expressed in units ofbarrers/mm, where “barrers/mm” is defined as [(cm³ oxygen)/(cm²)(sec)(mmHg)]×10⁻⁹.

The “ion permeability” through a lens correlates with the lonofluxDiffusion Coefficient. The lonoflux Diffusion Coefficient, D (in unitsof [mm²/min]), is determined by applying Fick's law as follows:

D=−n′/(A×dc/dx)

where n′=rate of ion transport [mol/min]; A=area of lens exposed [mm²];dc=concentration difference [mol/L]; dx=thickness of lens [mm].

“Ophthalmically compatible”, as used herein, refers to a material orsurface of a material which may be in intimate contact with the ocularenvironment for an extended period of time without significantlydamaging the ocular environment and without significant user discomfort.

The term “ophthalmically safe” with respect to a packaging solution forsterilizing and storing contact lenses is meant that a contact lensstored in the solution is safe for direct placement on the eye withoutrinsing after autoclave and that the solution is safe and sufficientlycomfortable for daily contact with the eye via a contact lens. Anophthalmically-safe packaging solution after autoclave has a tonicityand a pH that are compatible with the eye and is substantially free ofocularly irritating or ocularly cytotoxic materials according tointernational ISO standards and U.S. FDA regulations.

The invention is generally directed to a cost-effective andtime-efficient method for making silicone hydrogel contact lenses withdurable hydrophilic coatings by use of a water-soluble andthermally-crosslinkable hydrophilic polymeric material havingazetidinium groups.

The invention is partly based on the surprising discoveries that awater-soluble, azetidinium-containing, and thermally-crosslinkablehydrophilic polymeric material, which is a partial reaction product of apolyamine-epichlorohydrin or polyamidoamine-epichlorohydrin with atleast one hydrophilicity-enhancing agent having at least one reactivefunctional group selected from the group consisting of amino group,carboxyl group, thiol group, and combination thereof, can be used toform a crosslinked coating with a good surface hydrophilicity and/orwettability, a good hydrophilicity and a good intactness on a siliconehydrogel contact lens having carboxyl acid and/or amino groups at ornear its surface. At a relatively elevated temperature (defined above),positively-charged azetidinium groups react with functional groups suchas amino groups, thiol groups, and carboxylate ion —COO⁻ (i.e., thedeprotonated form of a carboxyl group) to form neutral,hydroxyl-containing covalent linkages as illustrated in the scheme I

in which R is the rest portion of a compound, L is —NR′— in which R′ ishydrogen, a C₁-C₂₀ unsubstituted or substituted, linear or branchedalkyl group or a polymer chain —S—, or —OC(═O)—. Because of thethermally-controllable reactivity of azetidinium groups,polyamine-epichlorohydrin or polyamidoamine-epichlorohydrin (PAE) hasbeen widely used as a wet-strengthening agent. However, PAE has not beensuccessfully used to form crosslinked coatings on contact lenses,probably because crosslinked PAE coatings may not be able to impartdesirable hydrophilicity, wettability, and lubricity to contact lenses.It is surprisingly discovered here that PAE can be chemically-modifiedwith a hydrophilicity-enhancing agent (especially a hydrophilic polymer)having one or more functional groups each capable of reacting with oneazetidinium group, in a “heat-pretreatment” or “pretreatment” process,to obtain a water-soluble, azetidinium-containing polymeric material.Such polymeric material, which is still thermally-crosslinkable(reactive) due to the presence of azetidinium groups, can be used toform a crosslinked coating on a silicone hydrogel contact lens havingreactive functional groups (e.g., amino groups, carboxyl groups, thiolgroups, or combinations thereof) on and/or near its surface. And, it issurprised to discover that resultant crosslinked coatings on the contactlens, derived from the water-soluble, azetidinium-containing polymericmaterial, has an improved surface hydrophilicity, wettability and/orlubricity relative to a control coating obtained either by using anunmodified (original or starting) PAE alone or by using a mixture of PAEand a hydrophilicity-enhancing agent (without undergoing the heatpretreatment for preparing the water-soluble, azetidinium-containingpolymeric material).

It is believed that a hydrophilicity-enhancing agent may play at leasttwo roles in increasing the performance of resultant crosslinkedcoatings: adding hydrophilic polymer chains onto a polyamine orpolyamidoamine polymer chain to form a highly-branched hydrophilicpolymeric material with dangling polymer chains and/or chain segments;and decreasing the crosslinking density of the crosslinked coating byreducing significantly the number of azetidinium groups of thecrosslinkable polymeric material (coating material). A coating with aloose structure and dangling polymer chains and/or chain segments isbelieved to impart a good surface hydrophilicity, wettability and/orlubricity.

The invention is also partly based on the discoveries that a crosslinkedcoating of the invention can be advantageously formed onto a siliconehydrogel contact lens directly in a lens package containing the contactlens immersed in a lens packaging solution in the presence of awater-soluble azetidinium-containing polymeric material. The presence ofthe azetidinium-containing polymeric material can be accomplished eitherby adding the azetidinium-containing polymeric material in the lenspackaging solution, or by, prior to packaging, depositing physically alayer of the azetidinium-containing polymeric material onto the surfaceof a contact lens at room temperature.

Typically, contact lenses, which are hydrated and packaged in apackaging solution, must be sterilized. Sterilization of the hydratedlenses during manufacturing and packaging is typically accomplished byautoclaving. The autoclaving process involves heating the packaging of acontact lens to a temperature of from about 118° C. to about 125° C. forapproximately 20-40 minutes under pressure. It is discovered that duringautoclave, a water-soluble, azetidinium-containing polymeric materialcan be crosslinked effectively with the functional groups (e.g., aminogroups, thiol groups, and/or carboxylic acid groups) on and/or near thesurface of a silicone hydrogel contact lens to form a crosslinkedcoating which are wettable and ophthalmically compatible. It is believedthat during autoclave those azetidinium groups which do not participatein crosslinking reaction may be hydrolyzed into 2,3-dihydroxypropyl(HO—CH₂—CH(OH)—CH₂—) groups and that the azetidinium-containingpolymeric material present in the lens packaging solution, ifapplicable, can be converted to a non-reactive polymeric wettingmaterial capable of improving a lens's insert comfort.

By using the method of the invention, the coating process can becombined with the sterilization step (autoclave) in the manufacturing ofsilicone hydrogel contact lenses. The resultant contact lenses not onlycan have a high surface hydrophilicity/wettability, no or minimalsurface changes, good intactness, and good durability, but also can beused directly from the lens package by a patient without washing and/orrising because of the ophthalmic compatibility of the packagingsolution.

The invention, in one aspect, provides a method for producing siliconehydrogel contact lenses each having a crosslinked hydrophilic coatingthereon, the method of invention comprising the steps of: (a) obtaininga silicone hydrogel contact lens and a water-soluble andthermally-crosslinkable hydrophilic polymeric material, wherein thecontact lens comprises amino and/or carboxyl groups on and/or near thesurface of the contact lens, wherein the hydrophilic polymeric materialcomprises (i) from about 20% to about 95% by weight of first polymerchains derived from an epichlorohydrin-functionalized polyamine orpolyamidoamine, (ii) from about 5% to about 80% by weight of hydrophilicmoieties or second polymer chains derived from at least onehydrophilicity-enhancing agent having at least one reactive functionalgroup selected from the group consisting of amino group, carboxyl group,thiol group, and combination thereof, wherein the hydrophilic moietiesor second polymer chains are covalently attached to the first polymerchains through one or more covalent linkages each formed between oneazetitdinium group of the epichlorohydrin-functionalized polyamine orpolyamidoamine and one amino, carboxyl or thiol group of thehydrophilicity-enhancing agent, and (iii) azetidinium groups which areparts of the first polymer chains or pendant or terminal groupscovalently attached to the first polymer chains; and (b) heating thecontact lens in an aqueous solution in the presence of the hydrophilicpolymeric material to and at a temperature from about 40° C. to about140° C. for a period of time sufficient to covalently attach thehydrophilic polymeric material onto the surface of the contact lensthrough second covalent linkages each formed between one azetidiniumgroup of the hydrophilic polymeric material and one of the amino and/orcarboxyl groups on and/or near the surface of the contact lens, therebyforming a crosslinked hydrophilic coating on the contact lens.

A person skilled in the art knows very well how to make contact lenses.For example, contact lenses can be produced in a conventional“spin-casting mold,” as described for example in U.S. Pat. No.3,408,429, or by the full cast-molding process in a static form, asdescribed in U.S. Pat. Nos. 4,347,198; 5,508,317; 5,583,463; 5,789,464;and 5,849,810. In cast-molding, a lens formulation typically isdispensed into molds and cured (i.e., polymerized and/or crosslinked) inmolds for making contact lenses. For production of silicone hydrogelcontact lenses, a lens formulation for cast-molding generally comprisesat least one components selected from the group consisting of asilicone-containing vinylic monomer, a silicone-containing vinylicmacromer, a silicone-containing prepolymer, a hydrophilic vinylicmonomer, a hydrophilic vinylic macromer, a hydrophobic vinylic monomer,and combination thereof, as well known to a person skilled in the art. Asilicone hydrogel contact lens formulation can also comprise othernecessary components known to a person skilled in the art, such as, forexample, a crosslinking agent, a UV-absorbing agent, a visibilitytinting agent (e.g., dyes, pigments, or mixtures thereof), antimicrobialagents (e.g., preferably silver nanoparticles), a bioactive agent,leachable lubricants, leachable tear-stabilizing agents, and mixturesthereof, as known to a person skilled in the art. Molded siliconehydrogel contact lenses then can be subjected to extraction with anextraction solvent to remove unpolymerized components from the moldedlenses and to hydration process, as known by a person skilled in theart. Numerous silicone hydrogel lens formulations have been described innumerous patents and patent applications published by the filing date ofthis application.

In accordance with the invention, a silicone hydrogel contact lens caneither inherently comprise or be modified to comprise amino groupsand/or carboxyl groups on and/or near its surface.

Where a silicone hydrogel contact lens inherently comprises amino groupsand/or carboxyl groups on and/or near its surface, it is obtained bypolymerizing a silicone hydrogel lens formulation comprising a reactivevinylic monomer.

Examples of preferred reactive vinylic monomers include withoutlimitation amino-C₂-C₆ alkyl(meth)acrylate, C₁-C₆ alkylamino-C₂-C₆alkyl(meth)acrylate, allylamine, vinylamine, amino-C₂-C₆alkyl(meth)acrylamide, C₁-C₆ alkylamino-C₂-C₆ alkyl(meth)acrylamide,acrylic acid, C₁-C₁₂ alkylacrylic acid (e.g., methacrylic ethylacrylicacid, propylacrylic acid, butylacrylic acid, etc.),N,N-2-acrylamidoglycolic acid, beta methyl-acrylic acid (crotonic acid),alpha-phenyl acrylic acid, beta-acryloxy propionic acid, sorbic acid,angelic acid, cinnamic acid, 1-carobxy-4-phenyl butadiene-1,3, itaconicacid, citraconic acid, mesaconic acid, glutaconic acid, aconitic acid,maleic acid, fumaric acid, tricarboxy ethylene, and combinationsthereof. Preferably, the silicone hydrogel contact lens is made from alens formulation comprising at least one reactive vinylic monomerselected from the group consisting of amino-C₂-C₆ alkyl(meth)acrylate,C₁-C₆ alkylamino-C₂-C₆ alkyl(meth)acrylate, allylamine, vinylamine,amino-C₂-C₆ alkyl (meth)acrylamide, C₁-C₆ alkylamino-C₂-C₆alkyl(meth)acrylamide, acrylic acid, C₁-C₁₂ alkylacrylic acid,N,N-2-acrylamidoglycolic acid, and combinations thereof. The lensformulation comprises preferably from about 0.1% to about 10%, morepreferably from about 0.25% to about 7%, even more preferably from about0.5% to about 5%, most preferably from about 0.75% to about 3%, byweight of the reactive vinylic monomer.

A silicone hydrogel contact lens can also be subjected either to asurface treatment to form a reactive base coating having amino groupsand/or carboxyl groups on the surface of the contact lens. Examples ofsurface treatments include without limitation a surface treatment byenergy (e.g., a plasma, a static electrical charge, irradiation, orother energy source), chemical treatments, chemical vapor deposition,the grafting of hydrophilic vinylic monomers or macromers onto thesurface of an article, layer-by-layer coating (“LbL coating”) obtainedaccording to methods described in U.S. Pat. Nos. 6,451,871, 6,719,929,6,793,973, 6,811,805, and 6,896,926 and in U.S. Patent ApplicationPublication Nos. 2007/0229758A1, 2008/0152800A1, and 2008/0226922A1,(herein incorporated by references in their entireties). “LbL coating”,as used herein, refers to a coating that is not covalently attached tothe polymer matrix of a contact lens and is obtained through alayer-by-layer (“LbL”) deposition of charged or chargeable (byprotonation or deprotonation) and/or non-charged materials on the lens.An LbL coating can be composed of one or more layers.

Preferably, the surface treatment is an LbL coating process. In thispreferred embodiment (i.e., the reactive LbL base coating embodiment), aresultant silicone hydrogel contact lens comprises a reactive LbL basecoating including at least one layer of a reactive polymer (i.e., apolymer having pendant amino groups and/or carboxyl groups), wherein thereactive LbL base coating is obtained by contacting the contact lenswith a solution of a reactive polymer. Contacting of a contact lens witha coating solution of a reactive polymer can occur by dipping it intothe coating solution or by spraying it with the coating solution. Onecontacting process involves solely dipping the contact lens in a bath ofa coating solution for a period of time or alternatively dipping thecontact lens sequentially in a series of bath of coating solutions for afixed shorter time period for each bath. Another contacting processinvolves solely spray a coating solution. However, a number ofalternatives involve various combinations of spraying- and dipping-stepsmay be designed by a person having ordinary skill in the art. Thecontacting time of a contact lens with a coating solution of a reactivepolymer may last up to about 10 minutes, preferably from about 5 toabout 360 seconds, more preferably from about 5 to about 250 seconds,even more preferably from about 5 to about 200 seconds.

In accordance with this reactive LbL base coating embodiment, thereactive polymer can be a linear or branched polymer having pendantamino groups and/or carboxyl groups. Any polymers having pendant aminogroups and/or carboxyl groups can be used as a reactive polymer forforming base coatings on silicone hydrogel contact lenses. Examples ofsuch reactive polymers include without limitation: a homopolymer of areactive vinylic monomer; a copolymer of two or more reactive vinylicmonomers; a copolymer of a reactive vinylic monomer with one or morenon-reactive hydrophilic vinylic monomers (i.e., hydrophilic vinylicmonomers free of any carboxyl or (primary or secondary) amino group);polyethyleneimine (PEI); polyvinylalcohol with pendant amino groups; acarboxyl-containing cellulose (e.g., carboxymethylcellulose,carboxyethylcellulose, carboxypropylcellulose); hyaluronate; chondroitinsulfate; poly(glutamic acid); poly(aspartic acid); and combinationsthereof.

Examples of preferred reactive vinylic monomers are those describedpreviously, with carboxylic acid-containing vinylic monomers as mostpreferred reactive vinylic monomers for preparing reactive polymers forforming a reactive LbL base coating.

Preferred examples of non-reactive hydrophilic vinylic monomers free ofcarboxyl or amino group include without limitation acrylamide (AAm),methacrylamide N,N-dimethylacrylamide (DMA), N,N-dimethylmethacrylamide(DMMA), N-vinylpyrrolidone (NVP), N,N,-dimethylaminoethylmethacrylate(DMAEM), N,N-dimethylaminoethylacrylate (DMAEA),N,N-dimethylaminopropylmethacrylamide (DMAPMAm),N,N-dimethylaminopropylacrylamide (DMAPAAm), glycerol methacrylate,3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide,N-[tris(hydroxymethyl)methyl]-acrylamide,N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,2-hydroxyethyl(meth)acrylate, hydroxypropyl(meth)acrylate, C₁-C₄-alkoxypolyethylene glycol (meth)acrylate having a weight average molecularweight of up to 1500 Daltons, N-vinyl formamide, N-vinyl acetamide,N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinylalcohol (hydrolyzed form of vinyl acetate in the copolymer), aphosphorylcholine-containing vinylic monomer (including(meth)acryloyloxyethyl phosphorylcholine and those described in U.S.Pat. No. 5,461,433, herein incorporated by reference in its entirety),and combinations thereof.

Preferably, the reactive polymers for forming a reactive LbL basecoating are polyacrylic acid, polymethacrylic acid, poly(C₂-C₁₂alkylacrylic acid), poly[acrylic acid-co-methacrylic acid],poly(N,N-2-acrylamidoglycolic acid), poly[(meth)acrylicacid-co-acrylamide], poly[(meth)acrylic acid-co-vinylpyrrolidone],poly[C₂-C₁₂ alkylacrylic acid-co-acrylamide], poly[C₂-C₁₂ alkylacrylicacid-co-vinylpyrrolidone], hydrolyzed poly[(meth)acrylicacid-co-vinylacetate], hydrolyzed poly[C₂-C₁₂ alkylacrylicacid-co-vinylacetate], polyethyleneimine (PEI), polyallylaminehydrochloride (PAH) homo- or copolymer, polyvinylamine homo- orcopolymer, or combinations thereof.

The weight average molecular weight M_(w) of a reactive polymer forforming a reactive LbL base coating is at least about 10,000 Daltons,preferably at least about 50,000 Daltons, more preferably from about100,000 Daltons to about 5,000,000 Daltons.

A solution of a reactive polymer for forming a reactive LbL base coatingon contact lenses can be prepared by dissolving one or more reactivepolymers in water, a mixture of water and one or more organic solventsmiscible with water, an organic solvent, or a mixture of one or moreorganic solvents. Preferably, the reactive polymer is dissolved in amixture of water and one or more organic solvents, an organic solvent,or a mixture of one or more organic solvent. It is believed that asolvent system containing at least one organic solvent can swell asilicone hydrogel contact lens so that a portion of the reactive polymermay penetrate into the silicone hydrogel contact lens and increase thedurability of the reactive base coating.

Any organic solvents can be used in preparation of a solution of thereactive polymer. Examples of preferred organic solvents include withoutlimitation tetrahydrofuran, tripropylene glycol methyl ether,dipropylene glycol methyl ether, ethylene glycol n-butyl ether, ketones(e.g., acetone, methyl ethyl ketone, etc.), diethylene glycol n-butylether, diethylene glycol methyl ether, ethylene glycol phenyl ether,propylene glycol methyl ether, propylene glycol methyl ether acetate,dipropylene glycol methyl ether acetate, propylene glycol n-propylether, dipropylene glycol n-propyl ether, tripropylene glycol n-butylether, propylene glycol n-butyl ether, dipropylene glycol n-butyl ether,tripropylene glycol n-butyl ether, propylene glycol phenyl etherdipropylene glycol dimethyl ether, polyethylene glycols, polypropyleneglycols, ethyl acetate, butyl acetate, amyl acetate, methyl lactate,ethyl lactate, i-propyl lactate, methylene chloride, methanol, ethanol,1- or 2-propanol, 1- or 2-butanol, tert-butanol, tert-amyl alcohol,menthol, cyclohexanol, cyclopentanol and exonorborneol, 2-pentanol,3-pentanol, 2-hexanol, 3-hexanol, 3-methyl-2-butanol, 2-heptanol,2-octanol, 2-nonanol, 2-decanol, 3-octanol, norborneol,2-methyl-2-pentanol, 2,3-dimethyl-2-butanol, 3-methyl-3-pentanol,1-methylcyclohexanol, 2-methyl-2-hexanol, 3,7-dimethyl-3-octanol,1-chloro-2-methyl-2-propanol, 2-methyl-2-heptanol, 2-methyl-2-octanol,2-2-methyl-2-nonanol, 2-methyl-2-decanol, 3-methyl-3-hexanol,3-methyl-3-heptanol, 4-methyl-4-heptanol, 3-methyl-3-octanol,4-methyl-4-octanol, 3-methyl-3-nonanol, 4-methyl-4-nonanol,3-methyl-3-octanol, 3-ethyl-3-hexanol, 3-methyl-3-heptanol,4-ethyl-4-heptanol, 4-propyl-4-heptanol, 4-isopropyl-4-heptanol,2,4-dimethyl-2-pentanol, 1-methylcyclopentanol, 1-ethylcyclopentanol,1-ethylcyclopentanol, 3-hydroxy-3-methyl-1-butene,4-hydroxy-4-methyl-1-cyclopentanol, 2-phenyl-2-propanol,2-methoxy-2-methyl-2-propanol 2,3,4-trimethyl-3-pentanol,3,7-dimethyl-3-octanol, 2-phenyl-2-butanol, 2-methyl-1-phenyl-2-propanoland 3-ethyl-3-pentanol, 1-ethoxy-2-propanol, 1-methyl-2-pyrrolidone,N,N-dimethylpropionamide, dimethyl formamide, dimethyl acetamide,dimethyl propionamide, N-methylpyrrolidinone, and mixtures thereof.

In another preferred embodiment, a silicone hydrogel comprisesinherently amino groups and/or carboxyl groups on and/or near itssurface and is further subjected to a surface treatment to form areactive LbL base coating having amino groups and/or carboxyl groupstherein.

In another preferred embodiment (reactive plasma base coating), asilicone hydrogel contact lens is subjected to a plasma treatment toform a covalently-attached reactive plasma base coating on the contactlens, i.e., polymerizing one or more reactive vinylic monomers (any oneof those described previously) under the effect of plasma generated byelectric discharge (so-called plasma-induced polymerization). The term“plasma” denotes an ionized gas, e.g. created by electric glow dischargewhich may be composed of electrons, ions of either polarity, gas atomsand molecules in the ground or any higher state of any form ofexcitation, as well as of photons. It is often called “low temperatureplasma”. For a review of plasma polymerization and its uses reference ismade to R. Hartmann “Plasma polymerisation: Grundlagen, Technik andAnwendung, Jahrb. Oberflächentechnik (1993) 49, pp. 283-296,Battelle-Inst. e.V. Frankfurt/Main Germany; H. Yasuda, “Glow DischargePolymerization”, Journal of Polymer Science: Macromolecular Reviews,vol. 16 (1981), pp. 199-293; H. Yasuda, “Plasma Polymerization”,Academic Press, Inc. (1985); Frank Jansen, “Plasma DepositionProcesses”, in “Plasma Deposited Thin Films”, ed. by T. Mort and F.Jansen, CRC Press Boca Raton (19); O. Auciello et al. (ed.)“Plasma-Surface Interactions and Processing of Materials” publ. byKluwer Academic Publishers in NATO ASI Series; Series E: AppliedSciences, vol. 176 (1990), pp. 377-399; and N. Dilsiz and G. Akovali“Plasma Polymerization of Selected Organic Compounds”, Polymer, vol. 37(1996) pp. 333-341. Preferably, the plasma-induced polymerization is an“after-glow” plasma-induced polymerization as described in WO98028026(herein incorporated by reference in its entirety). For “after-glow”plasma polymerization the surface of a contact lens is treated firstwith a non-polymerizable plasma gas (e.g. H2, He or Ar) and then in asubsequent step the surface thus activated is exposed to a vinylicmonomer having an amino group or carboxyl group (any reactive vinylicmonomer described above), while the plasma power having been switchedoff. The activation results in the plasma-induced formation of radicalson the surface which in the subsequent step initiate the polymerizationof the vinylic monomer thereon.

In accordance with the invention, a water-soluble andthermally-crosslinkable hydrophilic polymeric material containingazetidinium groups comprises (i.e., has a composition including) fromabout 20% to about 95%, preferably from about 35% to about 90%, morepreferably from about 50% to about 85%, by weight of first polymerchains derived from an epichlorohydrin-functionalized polyamine orpolyamidoamine and from about 5% to about 80%, preferably from about 10%to about 65%, even more preferably from about 15% to about 50%, byweight of hydrophilic moieties or second polymer chains derived from atleast one hydrophilicity-enhancing agent having at least one reactivefunctional group selected from the group consisting of amino group,carboxyl group, thiol group, and combination thereof. The composition ofthe hydrophilic polymeric material is determined by the composition(based on the total weight of the reactants) of a reactants mixture usedfor preparing the thermally-crosslinkable hydrophilic polymeric materialaccording to the crosslinking reactions shown in Scheme I above. Forexample, if a reactant mixture comprises about 75% by weight of anepichlorohydrin-functionalized polyamine or polyamidoamine and about 25%by weight of at least one hydrophilicity-enhancing agent based on thetotal weight of the reactants, then the resultant hydrophilic polymericmaterial comprise about 75% by weight of first polymer chains derivedfrom the epichlorohydrin-functionalized polyamine or polyamidoamine andabout 25% by weight of hydrophilic moieties or second polymer chainsderived from said at least one hydrophilicity-enhancing agent. Theazetidinium groups of the thermally-crosslinkable hydrophilic polymericmaterial are those azetidinium groups (of theepichlorohydrin-functionalized polyamine or polyamidoamine) which do notparticipate in crosslinking reactions for preparing thethermally-crosslinkable hydrophilic polymeric material.

An epichlorohydrin-functionalized polyamine or polyamidoamine can beobtained by reacting epichlorohydrin with a polyamine polymer or apolymer containing primary or secondary amino groups. For example, apoly(alkylene imines) or a poly(amidoamine) which is a polycondensatederived from a polyamine and a dicarboxylic acid (e.g., adipicacid-diethylenetriamine copolymers) can react with epichlorohydrin toform an epichlorohydrin-functionalized polymer. Similarly, a homopolymeror copolymer of aminoalkyl(meth)acrylate,mono-alkylaminoalkyl(meth)acrylate, aminoalkyl(meth)acrylamide, ormono-alkylaminoalkyl (meth)acrylamide can also react withepichlorohydrin to form an epichlorohydrin-functionalized polyamine. Thereaction conditions for epichlorohydrin-functionalization of a polyamineor polyamidoamine polymer are taught in EP1465931 (herein incorporatedby reference in its entirety). A preferredepichlorohydrin-functionalized polymer is polyaminoamide-epichlorohydrin(PAE) (or polyamide-polyamine-epichlorohydrin orpolyamide-epichlorohydrin), such as, for example, Kymene® or Polycup®resins (epichlorohydrin-functionalized adipic acid-diethylenetriaminecopolymers) from Hercules or Polycup® or Servamine® resins fromServo/Delden.

Any suitable hydrophilicity-enhancing agents can be used in theinvention so long as they contain at least one amino group, at least onecarboxyl group, and/or at least one thiol group.

A preferred class of hydrophilicity-enhancing agents include withoutlimitation: amino-, carboxyl- or thiol-containing monosaccharides (e.g.,3-amino-1,2-propanediol, 1-thiolglycerol, 5-keto-D-gluconic acid,galactosamine, glucosamine, galacturonic acid, gluconic acid,glucosaminic acid, mannosamine, saccharic acid 1,4-lactone, saccharideacid, Ketodeoxynonulosonic acid, N-methyl-D-glucamine,1-amino-1-deoxy-6-D-galactose, 1-amino-1-deoxysorbitol,1-methylamino-1-deoxysorbitol, N-aminoethyl gluconamide); amino-,carboxyl- or thiol-containing disaccharides (e.g., chondroitindisaccharide sodium salt, di(β-D-xylopyranosyl)amine, digalacturonicacid, heparin disaccharide, hyaluronic acid disaccharide, Lactobionicacid); and amino-, carboxyl- or thiol-containing oligosaccharides (e.g.,carboxymethyl-β-cyclodextrin sodium salt, trigalacturonic acid); andcombinations thereof.

Another preferred class of hydrophilicity-enhancing agents ishydrophilic polymers having one or more amino, carboxyl and/or thiolgroups. More preferably, the content of monomeric units having an amino(—NHR′ with R′ as defined above), carboxyl (—COOH) and/or thiol (—SH)group in a hydrophilic polymer as a hydrophilicity-enhancing agent isless than about 40%, preferably less than about 30%, more preferablyless than about 20%, even more preferably less than about 10%, by weightbased on the total weight of the hydrophilic polymer.

Another preferred class of hydrophilic polymers ashydrophilicity-enhancing agents are amino- or carboxyl-containingpolysaccharides, for example, such as, carboxymethylcellulose (having acarboxyl content of about 40% or less, which is estimated based on thecomposition of repeating units, —[C₆H_(10-m)O₅(CH₂CO₂H)_(m)]— in which mis 1 to 3), carboxyethylcellulose (having a carboxyl content of about36% or less, which is estimated based on the composition of repeatingunits, —[C₆H_(10-m)O₅(C₂H₄CO₂H)_(m)]— in which m is 1 to 3)carboxypropylcellulose (having a carboxyl content of about 32% or less,which is estimated based on the composition of repeating units,—[C₆H_(10-m)O₅(C₃H₆CO₂H)_(m)]—, in which m is 1 to 3), hyaluronic acid(having a carboxyl content of about 11%, which is estimated based on thecomposition of repeating units, —(C₁₃H₂₀O₉NCO₂H)—), chondroitin sulfate(having a carboxyl content of about 9.8%, which is estimated based onthe composition of repeating units, —(C₁₂H₁₈O₁₃NS CO₂H)—), orcombinations thereof.

Another preferred class of hydrophilic polymers ashydrophilicity-enhancing agents include without limitation:poly(ethylene glycol) (PEG) with one sole amino, carboxyl or thiol group(e.g., PEG-NH₂, PEG-SH, PEG-COOH); H₂N-PEG-NH₂; HOOC-PEG-COOH;HS-PEG-SH; H₂N-PEG-COOH; HOOC-PEG-SH; H₂N-PEG-SH; multi-arm PEG with oneor more amino, carboxyl and/or thiol groups; PEG dendrimers with one ormore amino, carboxyl and/or thiol groups; a diamino- ordicarboxyl-terminated homo- or co-polymer of a non-reactive hydrophilicvinylic monomer; a monoamino- or monocarboxyl-terminated homo- orco-polymer of a non-reactive hydrophilic vinylic monomer; a copolymerwhich is a polymerization product of a composition comprising (1) about50% by weight or less, preferably from about 0.1% to about 30%, morepreferably from about 0.5% to about 20%, even more preferably from about1% to about 15%, by weight of one or more reactive vinylic monomers and(2) at least one non-reactive hydrophilic vinylic monomer and/or atleast one phosphorylcholine-containing vinylic monomer; and combinationsthereof. Reactive vinylic monomer(s) and non-reactive hydrophilicvinylic monomer(s) are those described previously.

More preferably, a hydrophilic polymer as a hydrophilicity-enhancingagent is PEG-NH₂; PEG-SH; PEG-COOH; H₂N-PEG-NH₂; HOOC-PEG-COOH;HS-PEG-SH; H₂N-PEG-COOH; HOOC-PEG-SH; H₂N-PEG-SH; multi-arm PEG with oneor more amino, carboxyl or thiol groups; PEG dendrimers with one or moreamino, carboxyl or thiol groups; a monoamino-, monocarboxyl-, diamino-or dicarboxyl-terminated homo- or copolymer of a non-reactivehydrophilic vinylic monomer selected from the group consisting ofacryamide (AAm), N,N-dimethylacrylamide (DMA), N-vinylpyrrolidone (NVP),N-vinyl-N-methyl acetamide, glycerol (meth)acrylate,hydroxyethyl(meth)acrylate, N-hydroxyethyl(meth)acrylamide, C₁-C₄-alkoxypolyethylene glycol (meth)acrylate having a weight average molecularweight of up to 400 Daltons, vinyl alcohol,N-methyl-3-methylene-2-pyrrolidone, 1-methyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone,N,N-dimethylaminoethyl(meth)acrylate, N,N-dimethylaminopropyl(metha)crylamide, (meth)acryloyloxyethyl phosphorylcholine, andcombinations thereof; a copolymer which is a polymerization product of acomposition comprising (1) from about 0.1% to about 30%, preferably fromabout 0.5% to about 20%, more preferably from about 1% to about 15%, byweight of (meth)acrylic acid, C₂-C₁₂ alkylacrylic acid, vinylamine,allylamine and/or amino-C₂-C₄ alkyl(meth)acrylate, and (2)(meth)acryloyloxyethyl phosphorylcholine and/or at least onenon-reactive hydrophilic vinylic monomer selected from the groupconsisting of acryamide, N,N-dimethylacrylamide, N-vinylpyrrolidone,N-vinyl-N-methyl acetamide, glycerol (meth)acrylate,hydroxyethyl(meth)acrylate, N-hydroxyethyl (meth)acrylamide,C₁-C₄-alkoxy polyethylene glycol (meth)acrylate having a weight averagemolecular weight of up to 400 Daltons, vinyl alcohol, and combinationthereof.

Most preferably, the hydrophilicity-enhancing agent as ahydrophilicity-enhancing agent is PEG-NH₂; PEG-SH; PEG-COOH; monoamino-,monocarboxyl-, diamino- or dicarboxyl-terminated polyvinylpyrrolidone;monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminatedpolyacrylamide; monoamino-, monocarboxyl-, diamino- ordicarboxyl-terminated poly(DMA); monoamino- or monocarboxyl-, diamino-or dicarboxyl-terminated poly(DMA-co-NVP); monoamino-, monocarboxyl-,diamino- or dicarboxyl-terminated poly(NVP-co-N,N-dimethylaminoethyl(meth)acrylate)); monoamino-, monocarboxyl-, diamino- ordicarboxyl-terminated poly(vinylalcohol); monoamino-, monocarboxyl-,diamino- or dicarboxyl-terminated poly[(meth)acryloyloxyethylphosphrylcholine] homopolymer or copolymer; monoamino-, monocarboxyl-,diamino- or dicarboxyl-terminated poly(NVP-co-vinyl alcohol);monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminatedpoly(DMA-co-vinyl alcohol); poly[(meth)acrylic acid-co-acrylamide] withfrom about 0.1% to about 30%, preferably from about 0.5% to about 20%,more preferably from about 1% to about 15%, by weight of (meth)acrylicacid; poly[(meth)acrylic acid-co-NVP) with from about 0.1% to about 30%,preferably from about 0.5% to about 20%, more preferably from about 1%to about 15%, by weight of (meth)acrylic acid; a copolymer which is apolymerization product of a composition comprising (1)(meth)acryloyloxyethyl phosphorylcholine and (2) from about 0.1% toabout 30%, preferably from about 0.5% to about 20%, more preferably fromabout 1% to about 15%, by weight of a carboxylic acid containing vinylicmonomer and/or an amino-containing vinylic monomer; and combinationthereof.

PEGs with functional groups and multi-arm PEGs with functional groupscan be obtained from various commercial suppliers, e.g., Polyscience,and Shearwater Polymers, inc., etc.

Monoamino-, monocarboxyl-, diamino- or dicarboxyl-terminated homo- orcopolymers of one or more non-reactive hydrophilic vinylic monomers orof a phosphorylcholine-containing vinylic monomer can be preparedaccording to procedures described in U.S. Pat. No. 6,218,508, hereinincorporated by reference in its entirety. For example, to prepare adiamino- or dicarboxyl-terminated homo- or co-polymer of a non-reactivehydrophilic vinylic monomer, the non-reactive vinylic monomer, a chaintransfer agent with an amino or carboxyl group (e.g.,2-aminoethanethiol, 2-mercaptopropinic acid, thioglycolic acid,thiolactic acid, or other hydroxymercaptanes, aminomercaptans, orcarboxyl-containing mercaptanes) and optionally other vinylic monomerare copolymerized (thermally or actinically) with a reactive vinylicmonomer (having an amino or carboxyl group), in the presence of anfree-radical initiator. Generally, the molar ratio of chain transferagent to that of all of vinylic monomers other than the reactive vinylicmonomer is from about 1:5 to about 1:100, whereas the molar ratio ofchain transfer agent to the reactive vinylic monomer is 1:1. In suchpreparation, the chain transfer agent with amino or carboxyl group isused to control the molecular weight of the resultant hydrophilicpolymer and forms a terminal end of the resultant hydrophilic polymer soas to provide the resultant hydrophilic polymer with one terminal aminoor carboxyl group, while the reactive vinylic monomer provides the otherterminal carboxyl or amino group to the resultant hydrophilic polymer.Similarly, to prepare a monoamino- or monocarboxyl-terminated homo- orco-polymer of a non-reactive hydrophilic vinylic monomer, thenon-reactive vinylic monomer, a chain transfer agent with an amino orcarboxyl group (e.g., 2-aminoethanethiol, 2-mercaptopropinic acid,thioglycolic acid, thiolactic acid, or other hydroxymercaptanes,aminomercaptans, or carboxyl-containing mercaptanes) and optionallyother vinylic monomers are copolymerized (thermally or actinically) inthe absence of any reactive vinylic monomer.

As used herein, a copolymer of a non-reactive hydrophilic vinylicmonomer refers to a polymerization product of a non-reactive hydrophilicvinylic monomer with one or more additional vinylic monomers. Copolymerscomprising a non-reactive hydrophilic vinylic monomer and a reactivevinylic monomer (e.g., a carboxyl-containing vinylic monomer) can beprepared according to any well-known radical polymerization methods orobtained from commercial suppliers. Copolymers containingmethacryloyloxyethyl phosphorylcholine and carboxyl-containing vinylicmonomer can be obtained from NOP Corporation (e.g., LIPIDURE®-A and-AF).

The weight average molecular weight M_(w) of the hydrophilic polymerhaving at least one amino, carboxyl or thiol group (as ahydrophilicity-enhancing agent) is preferably from about 500 to about1,000,000, more preferably from about 1,000 to about 500,000.

In accordance with the invention, the reaction between ahydrophilicity-enhancing agent and an epichlorohydrin-functionalizedpolyamine or polyamidoamine is carried out at a temperature of fromabout 40° C. to about 100° C. for a period of time sufficient (fromabout 0.3 hour to about 24 hours, preferably from about 1 hour to about12 hours, even more preferably from about 2 hours to about 8 hours) toform a water-soluble and thermally-crosslinkable hydrophilic polymericmaterial containing azetidinium groups.

In accordance with the invention, the concentration of ahydrophilicity-enhancing agent relative to anepichlorohydrin-functionalized polyamine or polyamidoamine must beselected not to render a resultant hydrophilic polymeric materialwater-insoluble (i.e., a solubility of less than 0.005 g per 100 ml ofwater at room temperature) and not to consume more than about 99%,preferably about 98%, more preferably about 97%, even more preferablyabout 96% of the azetidinium groups of theepichlorohydrin-functionalized polyamine or polyamidoamine.

In accordance with the invention, the step of heating is performedpreferably by autoclaving the silicone hydrogel contact lens immersed ina packaging solution (i.e., a buffered aqueous solution) in a sealedlens package at a temperature of from about 118° C. to about 125° C. forapproximately 20-90 minutes. In accordance with this embodiment of theinvention, the packaging solution is a buffered aqueous solution whichis ophthalmically safe after autoclave.

Lens packages (or containers) are well known to a person skilled in theart for autoclaving and storing a soft contact lens. Any lens packagescan be used in the invention. Preferably, a lens package is a blisterpackage which comprises a base and a cover, wherein the cover isdetachably sealed to the base, wherein the base includes a cavity forreceiving a sterile packaging solution and the contact lens.

Lenses are packaged in individual packages, sealed, and sterilized(e.g., by autoclave at about 120° C. or higher for at least 30 minutes)prior to dispensing to users. A person skilled in the art willunderstand well how to seal and sterilize lens packages.

In accordance with the invention, a packaging solution contains at leastone buffering agent and one or more other ingredients known to a personskilled in the art. Examples of other ingredients include withoutlimitation, tonicity agents, surfactants, antibacterial agents,preservatives, and lubricants (or water-soluble viscosity builders)(e.g., cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone).

The packaging solution contains a buffering agent in an amountsufficient to maintain a pH of the packaging solution in the desiredrange, for example, preferably in a physiologically acceptable range ofabout 6 to about 8.5. Any known, physiologically compatible bufferingagents can be used. Suitable buffering agents as a constituent of thecontact lens care composition according to the invention are known tothe person skilled in the art. Examples are boric acid, borates, e.g.sodium borate, citric acid, citrates, e.g. potassium citrate,bicarbonates, e.g. sodium bicarbonate, TRIS(2-amino-2-hydroxymethyl-1,3-propanediol),Bis-Tris(Bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl)-methane),bis-aminopolyols, triethanolamine, ACES(N-(2-hydroxyethyl)-2-aminoethanesulfonic acid), BES(N,N-Bis(2-hydroxyethyl)-2-aminoethanesulfonic acid), HEPES(4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES(2-(N-morpholino)ethanesulfonic acid), MOPS(3-[N-morpholino]-propanesulfonic acid), PIPES(piperazine-N,N′-bis(2-ethanesulfonic acid), TES(N-[Tris(hydroxymethyl)methyl]-2-aminoethanesulfonic acid), saltsthereof, phosphate buffers, e.g. Na₂HPO₄, NaH₂PO₄, and KH₂PO₄ ormixtures thereof. A preferred bis-aminopolyol is1,3-bis(tris[hydroxymethyl]-methylamino)propane (bis-TRIS-propane). Theamount of each buffer agent in a packaging solution is preferably from0.001% to 2%, preferably from 0.01% to 1%; most preferably from about0.05% to about 0.30% by weight.

The packaging solution has a tonicity of from about 200 to about 450milliosmol (mOsm), preferably from about 250 to about 350 mOsm. Thetonicity of a packaging solution can be adjusted by adding organic orinorganic substances which affect the tonicity. Suitable occularlyacceptable tonicity agents include, but are not limited to sodiumchloride, potassium chloride, glycerol, propylene glycol, polyols,mannitols, sorbitol, xylitol and mixtures thereof.

A packaging solution of the invention has a viscosity of from about 1centipoise to about 20 centipoises, preferably from about 1.2centipoises to about 10 centipoises, more preferably from about 1.5centipoises to about 5 centipoises, at 25° C.

In a preferred embodiment, the packaging solution comprises preferablyfrom about 0.01% to about 2%, more preferably from about 0.05% to about1.5%, even more preferably from about 0.1% to about 1%, most preferablyfrom about 0.2% to about 0.5%, by weight of a water-soluble andthermally-crosslinkable hydrophilic polymeric material of the invention.

A packaging solution of the invention can contain a viscosity-enhancingpolymer. The viscosity-enhancing polymer preferably is nonionic.Increasing the solution viscosity provides a film on the lens which mayfacilitate comfortable wearing of the contact lens. Theviscosity-enhancing component may also act to cushion the impact on theeye surface during insertion and serves also to alleviate eyeirritation.

Preferred viscosity-enhancing polymers include, but are not limited to,water soluble cellulose ethers (e.g., methyl cellulose (MC), ethylcellulose, hydroxymethylcellulose, hydroxyethyl cellulose (HEC),hydroxypropylcellulose (HPC), hydroxypropylmethyl cellulose (HPMC), or amixture thereof), water-soluble polyvinylalcohols (PVAs), high molecularweight poly(ethylene oxide) having a molecular weight greater than about2000 (up to 10,000,000 Daltons), polyvinylpyrrolidone with a molecularweight of from about 30,000 daltons to about 1,000,000 daltons, acopolymer of N-vinylpyrrolidone and at least one dialkylaminoalkyl(meth)acrylate having 7-20 carbon atoms, and combinations thereof. Watersoluble cellulose ethers and copolymers of vinylpyrrolidone anddimethylaminoethylmethacrylate are most preferred viscosity-enhancingpolymers. Copolymers of N-vinylpyrrolidone anddimethylaminoethylmethacrylate are commercially available, e.g.,Copolymer 845 and Copolymer 937 from ISP.

The viscosity-enhancing polymer is present in the packaging solution inan amount of from about 0.01% to about 5% by weight, preferably fromabout 0.05% to about 3% by weight, even more preferably from about 0.1%to about 1% by weight, based on the total amount of the packagingsolution.

A packaging solution can further comprises a polyethylene glycol havinga molecular weight of about 1200 or less, more preferably 600 or less,most preferably from about 100 to about 500 daltons.

Where at least one of the crosslinked coating and the packaging solutioncontains a polymeric material having polyethylene glycol segments, thepackaging solution preferably comprises an α-oxo-multi-acid or saltthereof in an amount sufficient to have a reduced susceptibility tooxidation degradation of the polyethylene glycol segments. Acommonly-owned co-pending patent application (US patent applicationpublication No. 2004/0116564 A1, incorporated herein in its entirety)discloses that oxo-multi-acid or salt thereof can reduce thesusceptibility to oxidative degradation of a PEG-containing polymericmaterial.

Exemplary α-oxo-multi-acids or biocompatible salts thereof includewithout limitation citric acid, 2-ketoglutaric acid, or malic acid orbiocompatible (preferably ophthalmically compatible) salts thereof. Morepreferably, an α-oxo-multi-acid is citric or malic acid or biocompatible(preferably ophthalmically compatible) salts thereof (e.g., sodium,potassium, or the like).

In accordance with the invention, the packaging solution can furthercomprises mucin-like materials, ophthalmically beneficial materials,and/or surfactants.

Exemplary mucin-like materials include without limitation polyglycolicacid, polylactides, and the likes. A mucin-like material can be used asguest materials which can be released continuously and slowly overextended period of time to the ocular surface of the eye for treatingdry eye syndrome. The mucin-like material preferably is present ineffective amounts.

Exemplary ophthalmically beneficial materials include without limitation2-pyrrolidone-5-carboxylic acid (PCA), amino acids (e.g., taurine,glycine, etc.), alpha hydroxyl acids (e.g., glycolic, lactic, malic,tartaric, mandelic and citric acids and salts thereof, etc.), linoleicand gamma linoleic acids, and vitamins (e.g., B5, A, B6, etc.).

Surfactants can be virtually any ocularly acceptable surfactantincluding non-ionic, anionic, and amphoteric surfactants. Examples ofpreferred surfactants include without limitation poloxamers (e.g.,Pluronic® F108, F88, F68, F68LF, F127, F87, F77, P85, P75, P104, andP84), poloamines (e.g., Tetronic® 707, 1107 and 1307, polyethyleneglycol esters of fatty acids (e.g., Tween® 20, Tween® 80),polyoxyethylene or polyoxypropylene ethers of C₁₂-C₁₈ alkanes (e.g.,Brij® 35), polyoxyethyene stearate (Myrj® 52), polyoxyethylene propyleneglycol stearate (Atlas® G 2612), and amphoteric surfactants under thetrade names Mirataine® and Miranol®.

A silicone hydrogel contact lens obtained according a method of theinvention has a surface hydrophilicity/wettability characterized byhaving an averaged water contact angle of preferably about 90 degrees orless, more preferably about 80 degrees or less, even more preferablyabout 70 degrees or less, most preferably about 60 degrees or less.

In another preferred embodiment, a method of the invention can furthercomprise, before the step of heating, the steps of: contacting at roomtemperature the silicone hydrogel contact lens with an aqueous solutionof the thermally-crosslinkable hydrophilic polymeric material to form atop layer (i.e., an LbL coating) of the thermally-crosslinkablehydrophilic polymeric material on the surface of the silicone hydrogelcontact lens, immersing the silicone hydrogel contact lens with the toplayer of the thermally-crosslinkable hydrophilic polymeric material in apackaging solution in a lens package; sealing the lens package; andautoclaving the lens package with the silicone hydrogel contact lenstherein to form a crosslinked hydrophilic coating on the siliconehydrogel contact lens. Because of being positively charged, thethermally-crosslinkable hydrophilic polymeric material is believed to becapable of forming, on a silicone hydrogel contact lens, an LbL coatingwhich is not covalently bound to the surface of a silicone hydrogelcontact lens (i.e., through physical interactions), especially a contactlens having negatively-charged carboxyl groups on its surface.

It should be understood that although various embodiments includingpreferred embodiments of the invention may be separately describedabove, they can be combined and/or used together in any desirablefashion in the method of the invention for producing silicone hydrogelcontact lenses each having a crosslinked hydrophilic coating thereon.

In another aspect, the invention provides a silicone hydrogel contactlens obtained according to a method of invention described above.

In a further aspect, the invention provides an ophthalmic product, whichcomprises a sterilized and sealed lens package, wherein the lens packagecomprises a post-autoclave lens packaging solution and a readily-usablesilicone hydrogel contact lens immersed therein, wherein thereadily-usable silicone hydrogel contact lens comprises a crosslinkedhydrophilic coating obtained by autoclaving an original siliconehydrogel contact lens having amino groups and/or carboxyl groups onand/or near the surface of the original silicone hydrogel contact lensin a pre-autoclave packaging solution containing a water-soluble andthermally-crosslinkable hydrophilic polymeric material, wherein thehydrophilic polymeric material comprises (i) from about 20% to about95%, preferably from about 35% to about 90%, more preferably from about50% to about 85%, by weight of first polymer chains derived from anepichlorohydrin-functionalized polyamine or polyamidoamine, (ii) fromabout 5% to about 80%, preferably from about 10% to about 65%, even morepreferably from about 15% to about 50%, by weight of hydrophilicmoieties or second polymer chains derived from at least onehydrophilicity-enhancing agent having at least one reactive functionalgroup selected from the group consisting of amino group, carboxyl group,thiol group, and combination thereof, wherein the hydrophilic moietiesor second polymer chains are covalently attached to the first polymerchains through one or more covalent linkages each formed between oneazetitdinium group of the epichlorohydrin-functionalized polyamine orpolyamidoamine and one amino, carboxyl or thiol group of thehydrophilicity-enhancing agent, and (iii) azetidinium groups which areparts of the first polymer chains or pendant or terminal groupscovalently attached to the first polymer chains, wherein the hydrophilicpolymeric material is covalently attached onto the silicone hydrogelcontact lens through first covalent linkages each formed between oneamino or carboxyl group on and/or near the surface of the siliconehydrogel contact lens and one azetidinium group of thethermally-crosslinkable hydrophilic polymeric material, wherein thepost-autoclave packaging solution comprises at least one buffering agentin an amount sufficient to maintain a pH of from about 6.0 to about 8.5and has a tonicity of from about 200 to about 450 milliosmol (mOsm),preferably from about 250 to about 350 mOsm and a viscosity of fromabout 1 centipoise to about 20 centipoises, preferably from about 1.2centipoises to about 10 centipoises, more preferably from about 1.5centipoises to about 5 centipoises, at 25° C., wherein thepost-autoclave packaging solution comprises a polymeric wetting materialwhich is an hydrolyzed product of the thermally-crosslinkablehydrophilic polymeric material after autoclave, wherein thereadily-usable silicone hydrogel contact lens has a surfacehydrophilicity/wettability characterized by having an averaged watercontact angle of about 90 degrees or less, preferably about 80 degreesor less, more preferably about 70 degrees or less, even more preferablyabout 60 degrees or less, most preferably about 50 degrees or less.

A “readily-usable silicone hydrogel contact lens” refers to a siliconehydrogel contact lens which is ophthalmically compatible and sterilizedby autoclave. An “original silicone hydrogel contact lens” refers to asilicone hydrogel contact lens which lacks a crosslinked hydrophiliccoating and is not sterilized by autoclave.

Various embodiments including preferred embodiments of silicone hydrogelcontact lenses inherently having amino groups and/or carboxyl groups,silicone hydrogel contact lenses having a reactive base coating,reactive vinylic monomers, non-reactive vinylic monomers, reactivepolymers for forming a reactive LbL base coating, plasma coatings,epichlorohydrin-functionalized polyamine or polyamidoamine,hydrophilicity enhancing agents, water-soluble hydrophilic polymericmaterials with azetidinium groups, the step of heating, lens packages,packaging solutions, and surface wettability of a silicone hydrogelcontact lens with a crosslinked hydrophilic coating of the invention aredescribed above and can be combined and/or used together in these twoaspects of the invention.

A readily-usable silicone hydrogel contact lens of the invention has anoxygen permeability of at least about 40 barrers, preferably at leastabout 50 barrers, more preferably at least about 60 barrers, even morepreferably at least about 70 barrers; a center thickness of about 30 toabout 200 microns, more preferably about 40 to about 150 microns, evenmore preferably about 50 to about 120 microns, and most preferably about60 to about 110 microns; an elastic modulus of about 1.5 MPa or less,preferably about 1.2 MPa or less, more preferably about 1.0 or less,even more preferably from about 0.3 MPa to about 1.0 MPa; an lonofluxDiffusion Coefficient, D, of, preferably at least about 1.5×10⁻⁶mm²/min, more preferably at least about 2.6×10⁻⁶ mm²/min, even morepreferably at least about 6.4×10⁻⁶ mm²/min; a water content ofpreferably from about 18% to about 70%, more preferably from about 20%to about 60% by weight when fully hydrated; or combinations thereof.

The water content of a silicone hydrogel contact lens can be measuredaccording to Bulk Technique as disclosed in U.S. Pat. No. 5,849,811.

In a still further aspect, the invention provides a water-soluble andthermally-crosslinkable hydrophilic polymeric material, which comprises:(a) from about 20% to about 95%, preferably from about 35% to about 90%,more preferably from about 50% to about 85%, by weight of first polymerchains derived from an epichlorohydrin-functionalized polyamine orpolyamidoamine; (b) from about 5% to about 80%, preferably from about10% to about 65%, even more preferably from about 15% to about 50%, byweight of second polymer chains derived from at least onehydrophilicity-enhancing polymeric agent having at least one reactivefunctional group selected from the group consisting of amino group,carboxyl group, thiol group, and combination thereof, wherein the secondpolymer chains are covalently attached to the first polymer chainsthrough one or more covalent linkages each formed between oneazetitdinium group of the epichlorohydrin-functionalized polyamine orpolyamidoamine and one amino, carboxyl or thiol group of thehydrophilicity-enhancing polymeric agent; and (c) azetidinium groupswhich are parts of the first polymer chains or pendant groups covalentlyattached to the first polymer chains.

Various embodiments including preferred embodiments of reactive vinylicmonomers, non-reactive vinylic monomers, epichlorohydrin-functionalizedpolyamine or polyamidoamine, and hydrophilic polymers ashydrophilicity-enhancing agents are described above and can be combinedin any manner and/or used together in this aspect of the invention.

The previous disclosure will enable one having ordinary skill in the artto practice the invention. Various modifications, variations, andcombinations can be made to the various embodiment described herein. Inorder to better enable the reader to understand specific embodiments andthe advantages thereof, reference to the following examples issuggested. It is intended that the specification and examples beconsidered as exemplary.

Although various embodiments of the invention have been described usingspecific terms, devices, and methods, such description is forillustrative purposes only. The words used are words of descriptionrather than of limitation. It is to be understood that changes andvariations may be made by those skilled in the art without departingfrom the spirit or scope of the present invention, which is set forth inthe following claims. In addition, it should be understood that aspectsof the various embodiments may be interchanged either in whole or inpart or can be combined in any manner and/or used together. Therefore,the spirit and scope of the appended claims should not be limited to thedescription of the preferred versions contained therein.

Example 1 Oxygen Permeability Measurements

The apparent oxygen permeability of a lens and oxygen transmissibilityof a lens material is determined according to a technique similar to theone described in U.S. Pat. No. 5,760,100 and in an article by Wintertonet al., (The Cornea: Transactions of the World Congress on the Cornea111, H. D. Cavanagh Ed., Raven Press: New York 1988, pp273-280), both ofwhich are herein incorporated by reference in their entireties. Oxygenfluxes (J) are measured at 34° C. in a wet cell (i.e., gas streams aremaintained at about 100% relative humidity) using a Dk1000 instrument(available from Applied Design and Development Co., Norcross, Ga.), orsimilar analytical instrument. An air stream, having a known percentageof oxygen (e.g., 21%), is passed across one side of the lens at a rateof about 10 to 20 cm³/min., while a nitrogen stream is passed on theopposite side of the lens at a rate of about 10 to 20 cm³/min. A sampleis equilibrated in a test media (i.e., saline or distilled water) at theprescribed test temperature for at least 30 minutes prior to measurementbut not more than 45 minutes. Any test media used as the overlayer isequilibrated at the prescribed test temperature for at least 30 minutesprior to measurement but not more than 45 minutes. The stir motor'sspeed is set to 1200±50 rpm, corresponding to an indicated setting of400±15 on the stepper motor controller. The barometric pressuresurrounding the system, P_(measured), is measured. The thickness (t) ofthe lens in the area being exposed for testing is determined bymeasuring about 10 locations with a Mitotoya micrometer VL-50, orsimilar instrument, and averaging the measurements. The oxygenconcentration in the nitrogen stream (i.e., oxygen which diffusesthrough the lens) is measured using the DK1000 instrument. The apparentoxygen permeability of the lens material, Dk_(app), is determined fromthe following formula:

Dk _(app) =Jt/(P _(oxygen))

where J=oxygen flux [microliters O₂/cm²-minute]

P_(oxygen)=(P_(measured)−P_(water) vapor)=(%O₂ in air stream) [mmHg]=partial pressure of oxygen in the air stream

P_(measured)=barometric pressure (mm Hg)

P_(water) vapor=0 mm Hg at 34° C. (in a dry cell) (mm Hg)

P_(water) vapor=40 mm Hg at 34° C. (in a wet cell) (mm Hg)

t=average thickness of the lens over the exposed test area (mm)

Dk_(app) is expressed in units of barrers.

The apparent oxygen transmissibility (Dk/t) of the material may becalculated by dividing the apparent oxygen permeability (Dk_(app)) bythe average thickness (t) of the lens.

The above described measurements are not corrected for the so-calledboundary layer effect which is attributable to the use of a water orsaline bath on top of the contact lens during the oxygen fluxmeasurement. The boundary layer effect causes the reported value for theapparent Dk of a silicone hydrogel material to be lower than the actualintrinsic Dk value. Further, the relative impact of the boundary layereffect is greater for thinner lenses than with thicker lenses. The neteffect is that the reported Dk appear to change as a function of lensthickness when it should remain constant.

The intrinsic Dk value of a lens can be estimated based on a Dk valuecorrected for the surface resistance to oxygen flux caused by theboundary layer effect as follows.

Measure the apparent oxygen permeability values (single point) of thereference lotrafilcon A (Focus® N&D® from CIBA VISION CORPORATION) orlotrafilcon B (AirOptix™ from CIBA VISION CORPORATION) lenses using thesame equipment. The reference lenses are of similar optical power as thetest lenses and are measured concurrently with the test lenses.

Measure the oxygen flux through a thickness series of lotrafilcon A orlotrafilcon B (reference) lenses using the same equipment according tothe procedure for apparent Dk measurements described above, to obtainthe intrinsic Dk value (Dk_(i)) of the reference lens. A thicknessseries should cover a thickness range of approximately 100 μm or more.Preferably, the range of reference lens thicknesses will bracket thetest lens thicknesses. The Dk_(app) of these reference lenses must bemeasured on the same equipment as the test lenses and should ideally bemeasured contemporaneously with the test lenses. The equipment setup andmeasurement parameters should be held constant throughout theexperiment. The individual samples may be measured multiple times ifdesired.

Determine the residual oxygen resistance value, R_(r), from thereference lens results using equation 1 in the calculations.

$\begin{matrix}{R_{r} = \frac{\sum\left( {\frac{t}{{Dk}_{{app}\;}} - \frac{t}{{Dk}_{i}}} \right)}{n}} & (1)\end{matrix}$

In which t is the thickness of the test lens (i.e., the reference lenstoo), and n is the number of the reference lenses measured. Plot theresidual oxygen resistance value, R_(r) vs. t data and fit a curve ofthe form Y=a+bX where, for the jth lens, Y_(j)=(ΔP/J)_(j) and X=t_(j).The residual oxygen resistance, R_(r) is equal to a.

Use the residual oxygen resistance value determined above to calculatethe correct oxygen permeability Dk_(c) (estimated intrinsic Dk) for thetest lenses based on Equation 2.

Dk _(c) =t/[(t/Dk _(a))−R _(r)]  (2)

The estimated intrinsic Dk of the test lens can be used to calculatewhat the apparent Dk (Dk_(a) _(—) _(std)) would have been for a standardthickness lens in the same test environment based on Equation 3. Thestandard thickness (t_(std)) for lotrafilcon A=85 μm. The standardthickness for lotrafilcon B=60 μm.

Dk _(a) _(—) _(std) =t _(std)/[(t _(std) /Dk _(c))+R_(r) _(—)_(std)]  (3)

Ion Permeability Measurements.

The ion permeability of a lens is measured according to proceduresdescribed in U.S. Pat. No. 5,760,100 (herein incorporated by referencein its entirety. The values of ion permeability reported in thefollowing examples are relative ionoflux diffusion coefficients(D/D_(ref)) in reference to a lens material, Alsacon, as referencematerial. Alsacon has an ionoflux diffusion coefficient of 0.314×10⁻³mm²/minute.

Lubricity Evaluation

The lubricity rating is a qualitative ranking scheme where a scale of 0to 5 is used with 0 or lower numbers indicating better lubricity, 1 isassigned to Oasys™/TruEye™ commercial lenses and 5 is assigned tocommercial Air Optix™ lenses. The samples are rinsed with excess DIwater for at least three times and then transferred to PBS before theevaluation. Before the evaluation, hands are rinsed with a soapsolution, extensively rinsed with DI water and then dried with KimWipe®towels. The samples are handled between the fingers and a numericalnumber is assigned for each sample relative to the above standard lensesdescribed above. For example, if lenses are determined to be onlyslightly better than Air Optix™ lenses, then they are assigned a number4. For consistency, all ratings are independently collected by the sametwo operators in order to avoid bias and the data so far reveal verygood qualitative agreement and consistency in the evaluation.

Surface hydrophilicity/wetability Tests. Water contact angle on acontact lens is a general measure of the surface hydrophilicity (orwetability) of the contact lens. In particular, a low water contactangle corresponds to more hydrophilic surface. Average contact angles(Sessile Drop) of contact lenses are measured using a VCA 2500 XEcontact angle measurement device from AST, Inc., located in Boston,Mass. This equipment is capable of measuring advancing or recedingcontact angles or sessile (static) contact angles. The measurements areperformed on fully hydrated contact lenses and immediately afterblot-drying as follows. A contact lens is removed from the vial andwashed 3 times in ˜200 ml of fresh DI water in order to remove looselybound packaging additives from the lens surface. The lens is then placedon top of a lint-free clean cloth (Alpha Wipe TX1009), dabbed well toremove surface water, mounted on the contact angle measurement pedestal,blown dry with a blast of dry air and finally the sessile drop contactangle is automatically measured using the software provided by themanufacturer. The DI water used for measuring the contact angle has aresistivity >18 MΩcm and the droplet volume used is 2 μl. Typically,uncoated silicone hydrogel lenses (after autoclave) have a sessile dropcontact angle around 120 degrees. The tweezers and the pedestal arewashed well with Isopropanol and rinsed with DI water before coming incontact with the contact lenses.Water Break-up Time (WBUT) Tests. The wettabilty of the lenses (afterautoclave) is also assessed by determining the time required for thewater film to start breaking on the lens surface. Briefly, lenses areremoved from the vial and washed 3 times in ˜200 ml of fresh DI water inorder to remove loosely bound packaging additives from the lens surface.The lens is removed from the solution and held against a bright lightsource. The time that is needed for the water film to break (de-wet)exposing the underlying lens material is noted visually. Uncoated lensestypically instantly break upon removal from DI water and are assigned aWBUT of 0 seconds. Lenses exhibiting WBUT≧5 seconds are consideredwettable and are expected to exhibit adequate wettability (ability tosupport the tear film) on-eye.Coating Intactness Tests. The intactness of a coating on the surface ofa contact lens can be tested according to Sudan Black stain test asfollow. Contact lenses with a coating (an LbL coating, a plasma coating,or any other coatings) are dipped into a Sudan Black dye solution (SudanBlack in vitamin E oil). Sudan Black dye is hydrophobic and has a greattendency to be adsorbed by a hydrophobic material or onto a hydrophobiclens surface or hydrophobic spots on a partially coated surface of ahydrophobic lens (e.g., SiHy contact lens). If the coating on ahydrophobic lens is intact, no staining spots should be observed on orin the lens. All of the lenses under test are fully hydrated.Tests of coating durability. The lenses are digitally rubbed withSolo-care® multi-purpose lens care solution for 30 times and then rinsedwith saline. The above procedure is repeated for a given times, e.g.,from 1 to 30 times, (i.e., number of consecutive digital rubbing testswhich imitate cleaning and soaking cycles). The lenses are thensubjected to Sudan Black test (i.e., coating intactness test describedabove) to examine whether the coating is still intact. To survivedigital rubbing test, there is no significantly increased staining spots(e.g., staining spots covering no more than about 5% of the total lenssurface). Water contact angles are measured to determine the coatingdurability.Debris Adhesion Test. Contact lenses with a highly charged surface canbe susceptible to increased debris adhesion during patient handling. Apaper towel is rubbed against gloved hands and then both sides of thelens are rubbed with the fingers to transfer any debris to the lenssurface. The lens is briefly rinsed and then observed under amicroscope. A qualitative rating scale from 0 (no debris adhesion) to 4(debris adhesion equivalent to a PAA coated control lens) is used torate each lens. Lenses with a score of “0” or “1” are deemed to beacceptable.Surface Cracking Test. Excessive crosslinking of a coating layer canlead to surface cracks after rubbing a lens which are visible under adarkfield microscope. Lenses are inverted and rubbed and any crackinglines are noted. A qualitative rating of 0 (no cracking) to 2 (severecracking) is used to rate the lenses. Any severe cracking lines aredeemed unacceptable. Determination of azetidinium content. Theazetidinium content in PAE can be determined according to one of thefollowing assays.

PPVS assays. PAE charge density (i.e., azetidinium content) can bedetermined according to PPVS assay, a colorimetric titration assay wherethe titrant is potassium vinyl sulfate (PPVS) and Toluidine Blue is theindicator. See, S-K Kam and J. Gregory, “Charge determination ofsynthetic cationic polyelectrolytes by colloid titration,” in Colloid &Surface A: Physicochem. Eng. Aspect, 159: 165-179 (1999). PPVS bindspositively-charged species, e.g., Toluidine Blue and the azetidiniumgroups of PAE. Decreases in Toluidine Blue absorbance intensities areindicative of proportionate PAE charge density (azetidinium content).

PES-Na Assay. PES-Na assay is another colorimetric titration assay fordetermining PAE charge density (azetidinium content). In this assay, thetitrant is Sodium-polyethylensulphonate (PES-Na) instead of PPVS. Theassay is identical to the PPVS assay described above.

PCD assays. PCD assay is a potentiometric titration assay fordetermining PAE charge density (azetidinium content). The titrant isSodium-polyethylensulphonate (PES-Na), PPVS or other titrant. PAE chargeis detected by an electrode, for example using the Mütek PCD-04 ParticleCharge Detector from BTG. The measuring principle of this detector canbe found in BTG's websitehttp://www.btg.com/products.asp?langage=1&appli=5&numProd=357&cat=prod).

NMR method. Active positively charged moieties in PAE is azetidiniumgroups (AZRs). The NMR ratio method is a ratio of the number ofAZR-specific protons versus the number of non-AZR related protons. Thisratio is an indicator of the charge or AZR density for PAE.

Example 2 Preparation of CE-PDMS Macromer

In the first step, α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane(Mn=2000, Shin-Etsu, KF-6001a) is capped with isophorone diisocyanate(IPDI) by reacting 49.85 g ofα,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane with 11.1 g IPDI in150 g of dry methyl ethyl ketone (MEK) in the presence of 0.063 g ofdibutyltindilaurate (DBTDL). The reaction is kept for 4.5 h at 40° C.,forming IPDI-PDMS-IPDI. In the second step, a mixture of 164.8 g ofα,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane (Mn=3000, Shin-Etsu,KF-6002) and 50 g of dry MEK are added dropwise to the IPDI-PDMS-IPDIsolution to which has been added an additional 0.063 g of DBTDL. Thereactor is held for 4.5 h at about 40° C., formingHO-PDMS-IPDI-PDMS-IPDI-PDMS-OH. MEK is then removed under reducedpressure. In the third step, the terminal hydroxyl-groups are cappedwith methacryloyloxyethyl groups in a third step by addition of 7.77 gof isocyanatoethylmethacrylate (IEM) and an additional 0.063 g of DBTDL,forming IEM-PDMS-IPDI-PDMS-IPDI-PDMS-IEM (CE-PDMS macromer).

Alternate Preparation of CE-PDMS Macromer

240.43 g of KF-6001 is added into a 1-L reactor equipped with stirring,thermometer, cryostat, dropping funnel, and nitrogen/vacuum inletadapter, and then dried by application of high vacuum (2×10⁻² mBar).Then, under an atmosphere of dry nitrogen, 320 g of distilled MEK isthen added into the reactor and the mixture is stirred thoroughly. 0.235g of DBTDL is added to the reactor. After the reactor is warmed to 45°C., 45.86 g of IPDI are added through an addition funnel over 10 minutesto the reactor under moderate stirring. The reaction is kept for 2 hoursat 60° C. 630 g of KF-6002 dissolved in 452 g of distilled MEK are thenadded and stirred until a homogeneous solution is formed. 0.235 g ofDBTDL are added, and the reactor is held at about 55° C. overnight undera blanket of dry nitrogen. The next day, MEK is removed by flashdistillation. The reactor is cooled and 22.7 g of IEM are then chargedto the reactor followed by about 0.235 g of DBTDL. After about 3 hours,an additional 3.3 g of IEM are added and the reaction is allowed toproceed overnight. The following day, the reaction mixture is cooled toabout 18° C. to obtain CE-PDMS macromer with terminal methacrylategroups.

Example 3 Preparation of Lens Formulations

A lens formulation is prepared by dissolving components in 1-propanol tohave the following composition: 33% by weight of CE-PDMS macromerprepared in Example 2, 17% by weight ofN-[tris(trimethylsiloxy)-silylpropyl]acrylamide (TRIS-Am), 24% by weightof N,N-dimethylacrylamide (DMA), 0.5% by weight ofN-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-disteaoyl-sn-glycero-3-phosphoethanolamin, sodium salt)(L-PEG), 1.0% by weight Darocur 1173 (DC1173), 0.1% by weight ofvisitint (5% copper phthalocyanine blue pigment dispersion intris(trimethylsiloxy)silylpropylmethacrylate, TRIS), and 24.5% by weightof 1-propanol.

Preparation of Lenses

Lenses are prepared by cast-molding from the lens formulation preparedabove in a reusable mold, similar to the mold shown in FIGS. 1-6 in U.S.Pat. Nos. 7,384,590 and 7,387,759 (FIGS. 1-6). The mold comprises afemale mold half made of quartz (or CaF₂) and a male mold half made ofglass (or PMMA). The UV irradiation source is a Hamamatsu lamp with theWG335+TM297 cut off filter at an intensity of about 4 mW/cm². The lensformulation in the mold is irradiated with UV irradiation for about 25seconds. Cast-molded lenses are extracted with isopropanol (or methylethyl ketone, MEK), rinsed in water, coated with polyacrylic acid (PAA)by dipping lenses in a propanol solution of PAA (0.1% by weight,acidified with formic acid to about pH 2.5), and hydrated in water.Resultant lenses having a reactive PAA-LbL base coating thereon aredetermined to have the following properties: ion permeability of about8.0 to about 9.0 relative to Alsacon lens material; apparent Dk (singlepoint) of about 90 to 100; a water content of about 30% to about 33%;and an elastic modulus of about 0.60 MPa to about 0.65 MPa.

Example 4

An in-package coating (IPC) saline is prepared by adding 0.2%polyamidoamine-epichlorohydrin (PAE, Kymene) in phosphate buffer saline(PBS) and the pH is then adjusted to 7.2-7.4.

Lenses from Example 3 are placed in a polypropylene lens packaging shellwith 0.6 mL of the IPC saline (half of the IPC saline is added prior toinserting the lens). The blister is then sealed with foil and autoclavedfor about 30 minutes at 121° C., forming crosslinked coatings (PAA-x-PAEcoating) on the lenses.

Then the lenses are evaluated for debris adhesion, surface cracking,lubricity, contact angle and water break-up time (WBUT). The test lenses(packaged/autoclaved in the IPC saline, i.e., lenses having PAA-x-PAEcoating thereon) show no debris adhesion while control lenses(packaged/autoclaved in PBS, i.e., lenses having a PAA-LbL base coatingthereon) show severe debris adhesion. The water contact angle (WCA) ofthe test lenses is low (˜20 degrees) but the WBUT is less than 2seconds. When observed under dark field microscope, severe crackinglines are visible after handling the lens (lens inversion and rubbingbetween the fingers). The test lenses are much less lubricous than thecontrol lenses as judged by a qualitative finger-rubbing test (lubricityrating of 4).

Example 5

Poly(acrylamide-co-acrylic acid) partial sodium salt (˜80% solidcontent, Poly(AAm-co-AA)(80/20), Mw. 520,000, Mn 150,000) is purchasedfrom Aldrich and used as received.

An IPC saline is prepared by dissolving 0.02% of Poly(AAm-co-AA)(80/20)and 0.2% of PAE (Kymene) in PBS. The pH is adjusted to 7.2˜7.4. PBS isprepared by dissolving 0.76% NaCl, 0.044% NaH₂PO₄.H₂O and 0.388%Na₂HPO₄.2H₂O in water.

Lenses having a PAA-LbL base coating thereon prepared in Example 3 areplaced in a polypropylene lens packaging shell with 0.6 mL of the IPCsaline (half of the saline is added prior to inserting the lens). Theblister is then sealed with foil and autoclaved for about 30 minutes atabout 121° C. It is believed that a crosslinked coating composed ofthree layers PAA-x-PAE-x-poly(AAm-co-AA) is formed on the lenses duringautoclave.

The test lenses (packaged/autoclaved in the IPC saline, i.e., lenseshaving PAA-x-PAE-x-poly(AAm-co-AA) coating thereon) have no debrisadhesion and have a WBUT of longer than 10 seconds. When observed underdark field microscope, cracking lines are visible after rubbing the testlenses. The test lenses are much more lubricous than the test lensesfrom Example 4 but still not as lubricous as the control lenses packagedin PBS (lubricity rating of 1-2).

Example 6

An IPC saline is prepared by dissolving 0.02% of poly(AAm-co-AA) (80/20)and 0.2% of PAE (Kymene) in PBS and adjusting the pH to 7.2˜7.4. Thesaline is then treated by heating to and at about 70° C. for 4 hours(heat pre-treatment), forming a water-soluble andthermally-crosslinkable hydrophilic polymeric material containingazetidinium groups in the IPC saline. After the heat pre-treatment, theIPC saline is filtered using a 0.22 micron polyether sulphone (PES)membrane filter and cooled down back to room temperature.

Lenses having a PAA-LbL base coating thereon prepared in Example 3 areplaced in a polypropylene lens packaging shell with 0.6 mL of the IPCsaline (half of the saline is added prior to inserting the lens). Theblister is then sealed with foil and autoclaved for about 30 minutes atabout 121° C., forming a crosslinked coating (PAA-x-hydrophilicpolymeric material) on the lenses.

The test lenses (packaged in the heat-pretreated IPC saline, i.e.,lenses having PAA-x-hydrophilic polymeric material coating thereon) showno debris adhesion after being rubbed against paper towel while thecontrol lenses (packaged in PBS, i.e., lenses having a non-covalentlyattached layer of PAA thereon) show severe debris adhesion. The testlenses have a WBUT of longer than 10 seconds. When observed under darkfield microscope, no cracking lines are visible after rubbing the testlens. The test lenses are very lubricious in a finger rubbing test andequivalent to the control lenses (lubricity rating of 0).

A series of experiments are carried out to study the effects of theconditions (duration and/or temperature) of heat pre-treatment of theIPC saline upon the surface properties of resultant lenses coated withthe IPC saline. Depending on the azetidinium functionality of the PAEand the concentration of PAE used, heat treatment times of about 6 hoursor longer at about 70° C. result in lenses that are susceptible todebris adhesion similar to the control lenses. Heat treatment for only 4hours at 50° C. results in lenses that show surface cracking lines underdark field microscopy after being rubbed between the fingers similar tothe test lenses in Example 5 where the IPC saline is not heatpre-treated.

Example 7

Poly(acrylamide-co-acrylic acid) partial sodium salt (˜90% solidcontent, poly(AAm-co-AA) 90/10, Mw 200,000) is purchased fromPolysciences, Inc. and used as received.

An IPC saline is prepared by dissolving 0.07% of PAAm-PAA (90/10) and0.2% of PAE (Kymene) in PBS and adjusting the pH to 7.2˜7.4. Then thesaline is heat pre-treated for about 4 hours at about 70° C., forming awater-soluble and thermally-crosslinkable hydrophilic polymeric materialcontaining azetidinium groups. After the heat pre-treatment, the IPCsaline is filtered using a 0.22 micron polyether sulphone [PES] membranefilter and cooled down back to room temperature.

Lenses having a PAA-LbL base coating thereon prepared in Example 3 anduncoated Lotrafilcon B lenses (from CIBA VISION CORPORATION) that aredipped into an acidic propanol solution of PAA (ca. 0.1%, pH˜2.5) areplaced in a polypropylene lens packaging shells with 0.6 mL of theheat-pretreated IPC saline (half of the IPC saline is added prior toinserting the lens). The blister is then sealed with foil and autoclavedfor about 30 minutes at 121° C., forming a crosslinked coating(PAA-x-hydrophilic polymeric material) on the lenses.

The test lenses (both Lotrafilcon B and Example 3 lenses having aPAA-x-hydrophilic polymer thereon) have no debris adhesion. The testlenses have a WBUT of longer than 10 seconds. When observed under darkfield microscope, cracking lines are not visible after rubbing thelenses between the fingers. The lenses are extremely lubricous inqualitative finger rubbing tests (lubricity rating of 0).

Example 8

In design of experiments (DOE), IPC salines are produced to contain frombetween about 0.05% and about 0.09% PAAm-PAA and from about 0.075% toabout 0.19% PAE (Kymene) in PBS. The IPC salines are heat-treated for 8hours at 60° C. and lenses from Example 3 are packaged in theheat-pretreated IPC salines. No differences in the final lens surfaceproperties are observed and all lenses showed excellent lubricity,resistance to debris adhesion, excellent wettability, and no evidence ofsurface cracking.

Example 9

In design of experiments (DOE), IPC salines are produced to containabout 0.07% PAAm-PAA and sufficient PAE to provide an initialazetidinium content of approximately 9 millimole equivalents/Liter(˜0.15% PAE). The heat pre-treatment conditions are varied in a centralcomposite design from 50° C. to 70° C. and the pre-reaction time isvaried from about 4 to about 12 hours. A 24 hour pre-treatment time at60° C. is also tested. 10 ppm hydrogen peroxide is then added to thesalines to prevent bioburden growth and the IPC salines are filteredusing a 0.22 micron polyether sulphone [PES] membrane filter.

Lenses from Example 3 are packaged in the heat-pretreated IPC salinesand the blisters are then autoclaved for 45 minutes at 121° C. Alllenses have excellent lubricity, wettability, and resistance to surfacecracking. Some of the lenses show debris adhesion from paper towels asindicated in Table 1.

TABLE 1 Temperature (° C.) Time (hrs) 50 55 60 65 70 4 pass 6 pass pass8 pass pass fail 10 pass fail 12 pass 24 fail

Example 10

Copolymers of methacryloyloxyethyl phosphorylcholine (MPC) with onecarboxyl-containing vinylic monomer (CH₂═CH(CH₃)C(O)OC₂H₄OC(O)C₂H₄COOH(MS), methacrylic acid (MA)) in the absence or presence ofbutylmethacrylate (BMA) are evaluated in an in-package coating systemsin combination with PAE.

PBS containing NaCl (0.75% by weight), NaH₂PO₄.H2O (0.0536% by weight),Na₂HPO₄.2H₂O (0.3576% by weight) and DI water (97.59% by weight) isprepared and 0.2% PAE (polycup 3160) is added. The pH is adjusted toabout 7.3.

0.25% of one of several MPC copolymers is then added to form an IPCsaline and the IPC saline is heat pre-treated at 70° C. for 4 hours,forming a water-soluble thermally crosslinkable hydrophilic polymericmaterial containing azetidinium groups. After 4 hours, theheat-pretreated IPC saline is filtered through 0.2 micron Polyethersulphone [PES} membrane filters (Fisher Scientific catalog#09-741-04,Thermo Scientific nalgene #568-0020(250 ml).

Lenses having a PAA-LbL base coating thereon prepared in Example 3 arepackaged in the heat-pretreated IPC saline and autoclaved for about 30minutes at 121° C. Table 2 shows that all lenses possess excellentsurface properties.

TABLE 2 Crack- Lubric- Wettability MPC Copolymer* D. A. ing ity WBUT¹Poly(MPC/MA) 90/10 pass pass excellent excellent Poly(MPC/BMA/MA)40/40/20 pass pass excellent excellent Poly(MPC/BMA/MA) 70/20/10 passpass excellent excellent Poly(MPC/BMA/MS) 70/20/10 pass pass excellentexcellent *The numbers are molar percents of monomer units in thecopolymer D.A. = Debris Adhesion ¹“Excellent” means that WBUT is 10seconds or longer.

Example 11

PAA-coated lenses. Lenses cast-molded from a lens formulation preparedin Example 3 according to the molding process described in Example 3 areextracted and coated by dipping in the following series of baths: 3 MEKbaths (22, 78 and 224 seconds); DI water bath (56 seconds); 2 baths ofPAA coating solution (prepared by dissolving 3.6 g of PAA (M.W.: 450kDa, from Lubrizol) in 975 ml of 1-propanol and 25 ml of formic acid)for 44 and 56 seconds separately; and 3 DI water baths each for 56seconds.PAE/PAA-coated lenses. The above-prepared lenses with a PAA base coatingthereon are dipped successively into the following baths: 2 baths of PAEcoating solution, which is prepared by dissolving 0.25 wt % of PAE(Polycup 172, from Hercules) in DI water and adjusting the pH to about5.0 using sodium hydroxide and finally filtering the resultant solutionusing a 5 um filter, for 44 and 56 seconds respectively; and 3 baths ofDI water each for 56 seconds. After this treatment, the lenses have onelayer of PAA and one layer of PAE.Lenses with PAA-x-PAE-x-CMC coatings thereon. One batch of lenses withone layer of PAA and one layer of PAE thereon are packaged in a 0.2%Sodium carboxymethylcellulose (CMC, Product# 7H 3SF PH, Ashland Aqualon)in phosphate buffer saline (PBS) and the pH is then adjusted to 7.2-7.4.The blisters are then sealed and autoclaved for about 30 minutes at 121C., forming crosslinked coatings (PAA-x-PAE-x-CMC) on the lenses.Lenses with PAA-x-PAE-x-HA coatings thereon. Another batch of lenseswith one layer of PAA and one layer of PAE thereon are packaged in 0.2%Hyaluronic acid (HA, Product# 6915004, Novozymes) in phosphate buffersaline (PBS) and the pH is then adjusted to 7.2-7.4. The blisters arethen sealed and autoclaved for about 30 minutes at 121 C., formingcrosslinked coatings (PAA-x-PAE-x-HA) on the lenses.

The resultant lenses either with PAA-x-PAE-x-CMC coating or withPAA-x-PAE-x-HA coating thereon show no Sudan black staining, no debrisadhesion, and no cracking under microscopy examination. The lenses withPAA-x-PAE-x-CMC coating thereon have an average contact angle of 30±3degrees, while the lenses PAA-x-PAE-x-HA coating thereon have an averagecontact angle of with 20±3 degrees.

Example 12

IPC solution preparation. A reaction mixture is prepared by dissolving2.86% by weight of methoxy-poly(ethyleneglycol)-thiol, avg Mw 2000(Product #MPEG-5H-2000, Laysan Bio Inc.) along with 2% by weight of PAE(Kymene) in PBS and the final pH adjusted to 7.5. The solution isheat-treated for about 4 hours at 45° C. forming a thermallycrosslinkable hydrophilic polymeric material containing MPEG-SH-2000groups chemically grafted onto the polymer by reaction with theAzetidinium groups in PAE. After the heat-treatment, the solution isdiluted 10-fold with PBS containing 0.25% sodium citrate, pH adjusted to7.2˜7.4, and then filtered using 0.22 micron polyether sulphone (PES)membrane filter. The final IPC saline contains 0.286% by weight ofhydrophilic polymeric material (consisting of about 59% by weight ofMPEG-SH-2000 chains and about 41% by weight of PAE chains) and 0.25%Sodium citrate. PBS is prepared by dissolving 0.74% NaCl, 0.053%NaH₂PO₄.H₂O and 0.353% Na₂HPO₄.2H₂O in water.Lenses with crosslinked coatings thereon. PAA-coated lenses from Example11 are packaged in the above IPC saline in polypropylene lens packagingshells and then autoclaved for about 30 minutes at about 121° C.,forming a crosslinked coating on the lenses. The final lenses show nodebris adhesion, no cracking lines after rubbing the lens. The lensesare very lubricious in a finger rubbing test comparable to controlPAA-coated lenses.

A series of experiments are carried out to study the effects of theconditions (reaction time and solution concentration of mPEG-SH2000(with constant PAE concentration 2%) upon the surface properties of theresultant lenses coated with the IPC saline. The results are shown inTable 3.

TABLE 3 [mPEG- SH2000]¹ Reaction time Lubricity (wt %) @ 45° C. (hr)D.A. Cracking Test 1 Test 2 WCA 2.86 0 0.2 0.2; 2, NA 3 3 17 2.86 0.50.0 0.2; 0.2 2-3 2 21 2.86 2 0.0 0.0; 0.0 2 2 20 2.86 4 0.0 0.0; 0.0 1-21 37 0.5 4 0 0.2; NA 4 3-4 15 1.5 4 0 0.0; NA 3 3 20 6 4 0 0.0; NA 0-1 051 D.A. = debris adhesion; WCA = water contact angle. ¹PAEconcentration: 2% by weight.

As the solution concentration of mPEG-SH 2000 increases, the lenslubricity increases accordingly. It is believed that the increase in thecontact angle of the surface may be due to the increasing density ofterminal methyl groups on the surface with increasing grafting density.At high grafting densities, corresponding to a solution concentration of0.6%, the contact angle approaches measurements obtained on Polyethyleneglycol (PEG) monolayer grafted flat substrates (Reference: Langmuir2008, 24, 10646-10653).

Example 13

A series of experiments are carried out to study the effects ofmolecular weight of the mPEG-SH. The IPC saline is prepared similar tothe procedure described in Example 12, but using one of the followingmPEGSH: mPEG-SH 1000, mPEG-SH 2000, mPEG-SH 5000 and mPEG-SH 20000. Allthe salines are subjected to heat treatment at 45° C. for 4 hours and10-fold dilution. The results and the reaction conditions are shown inTable 4.

TABLE 4 mPEG-SH M.W. Lubricity (Daltons) Conc. (%)* D.A. Cracking Test 1Test 2 WCA 1000 1.5 No No 2 1 21 1000 2.86 No No 1 1 27 2000 1.5 No No 22 28 2000 2.86 No No 0-1 0 21 5000 1.5 No No 2 2 18 5000 2.86 No No 0-10-1 26 20000 1.5 No No 3 2 21 20000 2.86 No No 2 1 21 D.A. = debrisadhesion; WCA = water contact angle. *The initial concentration ofMPEG-SH in the IPC saline with 2% PAE therein before the heatpretreatment and the 10-fold dilution.

Example 14

A reaction mixture is prepared by dissolving 2.5% ofMethoxy-Poly(Ethylene Glycol)-Thiol, Avg MW 2000 (Product #MPEG-SH-2000,Laysan Bio Inc.), 10% of PAE (Kymene) in PBS and 0.25% of sodium citratedihydrate. The pH of this final solution is then adjusted to 7.5 andalso degassed to minimize thiol oxidation by bubbling nitrogen gasthrough the container for 2 hours. This solution is later heat treatedfor about 6 hours at 45° C. forming a thermally crosslinkablehydrophilic polymeric material containing MPEG-SH-2000 groups chemicallygrafted onto the polymer by reaction with the Azetidinium groups in PAE.After the heat-treatment, the solution is diluted 50-fold using PBScontaining 0.25% sodium citrate, pH adjusted to 7.2˜7.4, and thenfiltered using 0.22 micron polyether sulphone (PES) membrane filter. Thefinal IPC saline contains about 0.30% by weight of the polymericmaterial (consisting of about 17% wt.MPEG-SH-2000 and about 83% wt. PAE)and 0.25% Sodium citrate dihydrate.

PAA-coated lenses from Example 11 are packaged in the above IPC salinein polypropylene lens packaging shells and then autoclaved for about 30minutes at about 121° C., forming a crosslinked coating on the lenses.

The final lenses show no debris adhesion, no cracking lines afterrubbing the lens. The test lenses are very lubricious in a fingerrubbing test comparable to control PAA-coated lenses.

Example 15

A reaction mixture is prepared by dissolving 3.62% ofMethoxy-Poly(Ethylene Glycol)-Amine, Avg MW 550 (Product #MPEG-NH2-550,Laysan Bio Inc.) along with 2% of PAE (Kymene) in PBS and the final pHadjusted to 10. The solution is heat-treated for about 4 hours at 45° C.forming a thermally crosslinkable hydrophilic polymeric materialcontaining MPEG-NH2-550 groups chemically grafted onto the polymer byreaction with the Azetidinium groups in PAE. After the heat-treatment,the solution is diluted with 10-fold PBS containing 0.25% sodiumcitrate, pH adjusted to 7.2˜7.4, and then filtered using 0.22 micronpolyether sulphone (PES) membrane filter. The final IPC saline containsabout 0.562% wt. of polymeric material (consisting of 64% wt.MPEG-SH-2000 and about 36% wt. PAE) and 0.25% Sodium citrate dihydrate.The PBS is prepared by dissolving 0.74% Sodium chloride, 0.053%NaH₂PO₄.H₂O and 0.353% Na₂HPO₄.2H₂O in water.

PAA-coated lenses from Example 11 are packaged in the above IPC salinein polypropylene lens packaging shells and then autoclaved for about 30minutes at about 121° C., forming a crosslinked coating on the lenses.

The final lenses show no debris adhesion and no cracking lines afterrubbing the lens.

Example 16

Poloxamer 108 (sample) and nelfilcon A (CIBA VISION) are used asreceived. Nelfilcon A is a polymerizable polyvinyl alcohol obtained bymodifying a polyvinyl alcohol (e.g., Gohsenol KL-03 from Nippon Gohseior the like) with N-(2,2-Dimethoxyethyl)acrylamide under cyclic-acetalformation reaction conditions (Bühler et al., CHIMIA, 53 (1999),269-274, herein incorporated by reference in its entirety). About 2.5%of vinyl alcohol units in nelfilcon A is modified byN-(2,2-Dimethoxyethyl)acrylamide.

IPC saline is prepared by dissolving 0.004% poloxamer 108, 0.8%nelfilcon A, 0.2% PAE (Kymene, Polycup 3160), 0.45% NaCl, and 1.1%Na₂HPO₄.2H₂O in DI water. The saline is heat pre-treated by stirring for2 hrs at about 65-70° C. After heated pre-treatment, the saline isallowed to cool to room temperature and then filtered using a 0.2 μm PESfilter.

Lenses prepared in Example 3 are placed in a polypropylene lenspackaging shell with 0.6 mL of the IPC saline (half of the saline isadded prior to inserting the lens). The blister is then sealed with foiland autoclaved for about 30 minutes at 121° C.

The test lenses show no debris adhesion after being rubbed against papertowel. The lenses had a WBUT of above 10 seconds. When observed underdark foiled microscope, cracking lines are not visible after rubbing thelenses between the fingers. The lens is much more lubricous than thelenses from Example 4 but still not as lubricous as the control lensespackaged in PBS.

Example 17 A. Synthesis of 80% Ethylenically-FunctionalizedChain-Extended Polysiloxane

KF-6001A (α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane, Mn=2000,from Shin-Etsu) and KF-6002A(α,ω-bis(2-hydroxyethoxypropyl)-polydimethylsiloxane, Mn=3400, fromShin-Etsu) are separately dried at about 60° C. for 12 hours (orovernight) under high vacuum in a single neck flask. The OH molarequivalent weights of KF-6001A and KF-6002A are determined by titrationof hydroxyl groups and are used to calculate the millimolar equivalentto be used in the synthesis.

A one-liter reaction vessel is evacuated overnight to remove moisture,and the vacuum broken with dry nitrogen. 75.00 g (75 meq) of driedKF6001A is charged to the reactor, and then 16.68 g (150 meq) of freshlydistilled IPDI is added into the reactor. The reactor is purged withnitrogen and heated to 45° C. with stirring and then 0.30 g of DBTDL isadded. The reactor is sealed, and a positive flow of nitrogen ismaintained. An exotherm occurs, after which the reaction mixture isallowed to cool and stir at 55° C. for 2 hours. After reaching theexotherm, 248.00 g (150 meq) of dried KF6002A is added to the reactor at55° C. and then 100 μL of DBTDL is added. The reactor is stirred forfour hours. Heating is discontinued and the reactor is allowed to coolovernight. The nitrogen bubble is discontinued and the reactor is openedto atmosphere for 30 minutes with moderate stirring. Ahydroxyl-terminated chain-extended polysiloxane having 3 polysiloxanesegments, HO-PDMS-IPDI-PDMS-IPDI-PDMS-OH (or HO-CE-PDMS-OH), is formed.

For 80% ethylenically-functionalized polysiloxane, 18.64 g (120 meq) ofIEM is added to the reactor, along with 100 μL of DBTDL. The reactor isstirred for 24 hours, and then product (80% IEM-capped CE-PDMS) isdecanted and stored under refrigeration.

B: Synthesis of Non-UV-Absorbing Amphiphilic Branched PolysiloxanePrepolymer

A 1-L jacketed reactor is equipped with 500-mL addition funnel, overheadstirring, reflux condenser with nitrogen/vacuum inlet adapter,thermometer, and sampling adapter. The reactor is charged with 45.6 g of80% IEM-capped CE-PDMS prepared above and sealed. A solution of 0.65 gof hydroxyethyl methacrylate (HEMA), 25.80 g of DMA, 27.80 g of(tris(trimethylsilyl))-siloxypropyl)methacrylate (TRIS), in 279 g ofethyl acetate is charged to the addition funnel. The reactor is degassedat <1 mbar for 30 minutes at RT with a high-vacuum pump. The monomersolution is degassed at 100 mbar and RT for 10 minutes for three cycles,breaking vacuum with nitrogen between degas cycles. The monomer solutionis then charged to the reactor, and then the reaction mixture is stirredand heated to 67° C. While heating, a solution of 1.50 g ofmercaptoethanol (chain transfer agent, CTA) and 0.26 g ofazoisobutyronitrile dissolved in 39 g of ethyl acetate is charged to theaddition funnel and deoxygenated three times at 100 mbar, RT for 10minutes. When the reactor temperature reaches 67° C., the initiator/CTAsolution is added to the PDMS/monomer solution in the reactor. Thereaction is allowed to proceed for 8 hours, and then heating isdiscontinued and reactor temperature is brought to room temperaturewithin 15 minutes.

The resultant reaction mixture then is siphoned to a dry single-neckflask with airtight lid, and 4.452 g of IEM is added with 0.21 g ofDBTDL. The mixture is stirred 24 hs at room temperature, formingnon-UV-absorbing amphiphilic branched polysiloxane prepolymer. To thismixture solution, 100 uL of hydroxy-tetramethylene piperonyloxy solutionin ethyl acetate (2 g/20 mL) is added. The solution is then concentratedto 200 g (˜50%) using rota-yap at 30° C. and filtered through 1 um poresize filter paper. After solvent exchange to 1-propanol, the solution isfurther concentrated to the desired concentration.

C. Synthesis of UV-Absorbing Amphiphilic Branched PolysiloxanePrepolymer

A 1-L jacketed reactor is equipped with 500-mL addition funnel, overheadstirring, reflux condenser with nitrogen/vacuum inlet adapter,thermometer, and sampling adapter. The reactor is then charged with45.98 g of 80% IEM-capped CE-PDMS prepared above and the reactor issealed. A solution of 0.512 g of HEMA, 25.354 g of DMA, 1.38 g ofNorbloc methacrylate, 26.034 g of TRIS, in 263 g of ethyl acetate ischarged to the addition funnel. The reactor is degassed at <1 mbar for30 minutes at RT with a high-vacuum pump. The monomer solution isdegassed at 100 mbar and RT for 10 minutes for three cycles, breakingvacuum with nitrogen between degas cycles. The monomer solution is thencharged to the reactor, and then the reaction mixture is stirred andheated to 67° C. While heating, a solution of 1.480 g of mercaptoethanol(chain transfer agent, CTA) and 0.260 g of azoisobutyronitrile dissolvedin 38 g of ethyl acetate is charged to the addition funnel anddeoxygenated three times at 100 mbar, room temperature for 10 minutes.When the reactor temperature reaches 67° C., the initiator/CTA solutionis added to the PDMS/monomer solution in the reactor. The reaction isallowed to proceed for 8 hours, and then heating is discontinued andreactor temperature is brought to room temperature within 15 minutes.

The resultant reaction mixture then is siphoned to a dry single-neckflask with airtight lid, and 3.841 g of isocyanatoethyl acrylate isadded with 0.15 g of DBTDL. The mixture is stirred for about 24 hours atroom temperature, forming a UV-absorbing amphiphilic branchedpolysiloxane prepolymer. To this mixture solution, 100 uL ofhydroxy-tetramethylene piperonyloxy solution in ethyl acetate (2 g/20mL) is added. The solution is then concentrated to 200 g (˜50%) usingrota-yap at 30° C. and filtered through 1 um pore size filter paper.

D-1: Lens Formulation with Non-UV-Absorbing Polysiloxane Prepolymer

In a 100 mL amber flask, 4.31 g of synthesized macromer solutionprepared in Example C-2 (82.39% in 1-propanol) is added. In a 20 mLvial, 0.081 g of TPO and 0.045 g of DMPC are dissolved in 10 g of1-propanol and then transferred to the macromer solution. After themixture is concentrated to 5.64 g using rota-yap at 30° C., 0.36 g ofDMA is added and the formulation is homogenized at room temperature. 6 gof clear lens formulation D-1 is obtained.

D-2: Lens Formulation with UV-Absorbing Polysiloxane Prepolymer (4% DMA)

In a 100 mL amber flask, 24.250 g of macromer solution prepared inExample D-2 (43.92% in ethyl acetate) is added. In a 50 mL vial, 0.15 gof TPO and 0.75 g of DMPC is dissolved in 20 g of 1-propanol and thentransferred to the macromer solution. 20 g of solvent is pulled offusing rota-vap at 30° C., followed by addition of 20 g of 1-propanol.After two cycles, the mixture is concentrated to 14.40 g. 0.6 g of DMAis added to this mixture and the formulation is homogenized at roomtemperature. 15 g of clear lens formulation D-2 is obtained.

D-3: Lens Formulation with UV-Absorbing Polysiloxane Prepolymer (2%DMA/2% HEA)

In a 100 mL amber flask, 24.250 g of macromer solution prepared inExample D-2 (43.92% in ethyl acetate) is added. In a 50 mL vial, 0.15 gof TPO and 0.75 g of DMPC is dissolved in 20 g of 1-propanol and thentransferred to the macromer solution. 20 g of solvent is pulled offusing rota-vap at 30° C., followed by addition of 20 g of 1-propanol.After two cycles, the mixture is concentrated to 14.40 g. 0.3 g of DMAand 0.3 g of HEA is added to this mixture and the formulation ishomogenized at room temperature. 15 g of clear lens formulation D-3 isobtained.

Example 18 E: Covalent Attachment of Modified PAE Coating Polymers

Monomers containing amine groups, N-(3-Aminopropyl)methacrylamidehydrochloride (APMAA-HCl) or N-(2-aminoethyl)methacrylamidehydrochloride (AEMAA-HCl) are purchased from Polysciences and used asreceived. Poly(amidoamine epichlorohydrine) (PAE) is received fromAshland as an aqueous solution and used as received.Poly(acrylamide-co-acrylic acid) (poly(AAm-co-AA) (90/10) fromPolysciences, mPEG-SH from Laysan Bio, and poly(MPC-co-AeMA) (i.e., acopolymer of methacryloyloxyethyl phosphorylcholine (MPC) andaminoethylmethacrylate (AeMA)) from NOF are used as received.

APMAA-HCl monomer is dissolved in methanol and added to the lensformulations D-1, D-2 and D-3 (prepared in Example 17) to achieve a 1 wt% concentration.

Reactive packaging saline is prepared by dissolving the componentslisted in Table 5 along with appropriate buffer salts in DI water. Afterheated pre-treatment, the saline is allowed to cool to room temperatureand then filtered using a 0.2 μm PES filter.

TABLE 5 Package Saline Sample 1 2 3 4 5 pH 7.4  7.4 7.4 8 8 PAE  0.2%0.2% 0.2% 0.2% 0.2% Poly(AAm-co-AA) (90/10) 0.07% 0.2% — — — mPEG-SH, Mw= 2000 — — 0.3% — — mPEG-SH, Mw = 10000 — — — 0.2% — Poly(MPC-Co-AeMA)(90/10) — — — — 0.2% Pre-reaction condition 70° C., 70° C., 45° C., 45°C., 65° C., 4 h 4 h 4 h 4 h 2 h

Lens formulation D-1, D-2 and D3 prepared in Example 17 is modified byaddition of the APMAA-HCl monomer (stock solution of APMMA-HCL inmethanol). DSM lens is cured at 16 mW/cm² with 330 nm filter while LSlens is cured at 4.6 mW/cm² with 380 nm filter.

DSM lenses. Female portions of polypropylene lens molds are filled withabout 75 microliters of a lens formulation prepared as above, and themolds are closed with the male portion of the polypropylene lens molds(base curve molds). Contact lenses are obtained by curing the closedmolds for about 5 minutes with an UV irradiation source (Hamamatsu lampwith a 330 nm-cut-off filter at an intensity of about 16 mW/cm².

LS lenses. LS lenses are prepared by cast-molding from a lensformulation prepared as above in a reusable mold, similar to the moldshown in FIGS. 1-6 in U.S. Pat. Nos. 7,384,590 and 7,387,759 (FIGS.1-6). The mold comprises a female mold half made of quartz (or CaF₂) anda male mold half made of glass (or PMMA). The UV irradiation source is aHamamatsu lamp with a 380 nm-cut-off filter at an intensity of about 4.6mW/cm². The lens formulation in the mold is irradiated with UVirradiation for about 30 seconds.

Lens formulation D-1 modified with APMAA-HCl is cured according to DSMand LS methods described above, while with lens formulation D-2 or D-3is cured according to the LS method described above.

Molded lenses are extracted in methyl ethyl ketone, hydrated, andpackaged in one of the salines described in Table 5. Lenses are placedin a polypropylene lens packaging shell with 0.6 mL of the IPC saline(half of the saline is added prior to inserting the lens). The blisteris then sealed with foil and autoclaved for 30 min at 121° C.

Evaluation of the lens surface shows that all test lenses had no debrisadhesion. When observed under dark-field microscope, cracking lines arenot visible after rubbing the lenses between the fingers.

The lens surface wettability (WBUT), lubricity, and contact angle aremeasured and results are summarized in Table 6. The lenses are madeaccording DSM method unless specified otherwise. Lubricity is ratedagainst a qualitative scale from 0 to 4 where lower numbers indicategreater lubricity. In general, lens surface properties are somewhatimproved after application of the in-package coating

TABLE 6 Lens formulation for WBUT Contact making lenses Saline¹ (second)Lubricity Angle [°] D1 as control 1 0 4-5  114 (free of APMAA) 3 0 4 119D1 w/1%) APMAA 1 10  0-1  104 3 2 0-1   99 D2 as control 1 0 4-5  115(free of APMAA) 3 0 3 107 4  0² 3-4²  116² D2 w/1% APMAA 1 5 2-3   90 36 1  95 4 5-10²      3²  106² D3 as control 1  1² 3-4²  105² (free ofAPMAA) 2  5² 3-4²  94² 3  0²    3²  112² 4 12²    3²   36² 5  4²    3² 102² D3 w/1% APMAA 1  0²    4²  103² 2  9² 3-4²   97² 3 14² 2-3²   91²4 15²    3²   54² 5 13²    2²   69² ¹The number is the packaging salinenumber shown in Table 5. ²LS lenses.

Example 19

Lenses are fabricated using lens formulation D-2 (Example 17) to whichAPMAA monomer has been added to a concentration of 1%. LS lenses areprepared by cast-molding from a lens formulation prepared as above in areusable mold, similar to the mold shown in FIGS. 1-6 in U.S. Pat. Nos.7,384,590 and 7,387,759 (FIGS. 1-6). The mold comprises a female moldhalf made of glass and a male mold half made of quartz. The UVirradiation source is a Hamamatsu lamp with a 380 nm-cut-off filter atan intensity of about 4.6 mW/cm². The lens formulation in the mold isirradiated with UV irradiation for about 30 seconds.

Cast-molded lenses are extracted with methyl ethyl ketone (MEK), rinsedin water, coated with polyacrylic acid (PAA) by dipping lenses in apropanol solution of PAA (0.0044% by weight, acidified with formic acidto about pH 2.5), and hydrated in water.

IPC Saline is prepared according to the composition described in Example9 with pre-reaction conditions of 8 hrs at approximately 60° C. Lensesare placed in a polypropylene lens packaging shell with 0.6 mL of theIPC saline (half of the saline is added prior to inserting the lens).The blister is then sealed with foil and autoclaved for 30 min at 121°C.

Evaluation of the lens surface shows that all test lenses have no debrisadhesion. When observed under dark-field microscope, cracking lines arenot visible after rubbing the lenses between the fingers. The lenssurface wettability (WBUT) is greater than 10 seconds, lubricity israted as “1”, and contact angle is approximately 20°.

Example 20 Preparation of Lens Formulations

A lens formulation is prepared by dissolving components in 1-propanol tohave the following composition: about 32% by weight of CE-PDMS macromerprepared in Example 2, about 21% by weight of TRIS-Am, about 23% byweight of DMA, about 0.6% by weight of L-PEG, about 1% by weight ofDC1173, about 0.1% by weight of visitint (5% copper phthalocyanine bluepigment dispersion in TRIS), about 0.8% by weight of DMPC, about 200 ppmH-tempo, and about 22% by weight of 1-propanol.

Preparation of Lenses. Lenses are Prepared by Cast-Molding from the LensFormulation prepared above in a reusable mold (quartz female mold halfand glass male mold half), similar to the mold shown in FIGS. 1-6 inU.S. Pat. Nos. 7,384,590 and 7,387,759 (FIGS. 1-6). The lens formulationin the molds is irradiated with UV irradiation (13.0 mW/cm²) for about24 seconds. PAA-coating solution. A PAA coating solution is prepared bydissolving an amount of PAA (M.W.: 450 kDa, from Lubrizol) in a givenvolume of 1-propanol to have a concentration of about 0.36-0.44% byweight and the pH is adjusted with formic acid to about 1.7-2.3.PAA-coated lenses. Cast-molded contact lenses as above are extracted andcoated by dipping in the following series of baths: DI water bath (about56 seconds); 6 MEK baths (about 44, 56, 56, 56, 56, and 56 secondrespectively); DI water bath (about 56 seconds); one bath of PAA coatingsolution (about 0.36-0.44% by weight, acidified with formic acid toabout pH 1.7-2.3) in 100% 1-propanol (about 44 seconds); one bath of awater/1-propanol 50%/50% mixture (about 56 seconds); 4 DI water bathseach for about 56 seconds; one PBS bath for about 56 seconds; and one DIwater bath for about 56 seconds.IPC saline. Poly(AAm-co-AA)(90/10) partial sodium salt (˜90% solidcontent, poly(AAm-co-AA) 90/10, Mw 200,000) is purchased fromPolysciences, Inc. and used as received. PAE (Kymene, an azetidiniumcontent of 0.46 assayed with NMR) is purchased from Ashland as anaqueous solution and used as received. An IPC saline is prepared bydissolving about 0.07% w/w of poly(AAm-co-AA)(90/10) and about 0.15% ofPAE (an initial azetidinium millimolar equivalents of about 8.8millimole) in PBS (about 0.044 w/w % NaH₂PO₄.H₂O, about 0.388 w/w/%Na₂HPO₄.2H₂O, about 0.79 w/w % NaCl) and adjusting the pH to 7.2˜7.4.Then the IPC saline is heat pre-treated for about 4 hours at about 70°C. (heat pretreatment) During this heat pretreatment, poly(AAm-co-AA)and PAE are partially crosslinked to each other (i.e., not consuming allazetidinium groups of PAE) to form a water-soluble andthermally-crosslinkable hydrophilic polymeric material containingazetidinium groups within the branched polymer network in the IPCsaline. After the heat pre-treatment, the IPC saline is filtered using a0.22 micron polyether sulphone [PES] membrane filter and cooled downback to room temperature. 10 ppm hydrogen peroxide is then added to thefinal IPC saline to prevent bioburden growth and the IPC saline isfiltered using a 0.22 micron PES membrane filter. Application ofcrosslinked coating. Lenses having a PAA-LbL base coating thereonprepared above are placed in polypropylene lens packaging shells (onelens per shell) with 0.6 mL of the IPC saline (half of the saline isadded prior to inserting the lens). The blisters are then sealed withfoil and autoclaved for about 30 minutes at about 121° C., forming SiHycontact lenses with crosslinked coatings (PAA-x-hydrophilic polymericmaterial) thereon. Characterization of SiHy lenses. The resultant SiHycontact lenses with crosslinked coatings (PAA-x-hydrophilic polymericmaterial) thereon show no debris adhesion after being rubbed againstpaper towel while the control lenses (packaged in PBS, i.e., lenseshaving a non-covalently attached layer of PAA thereon) show severedebris adhesion. The lenses have an oxygen permebility (Dk_(c) orestimated intrinsic Dk) of about 146 barrers, a bulk elastic modulus ofabout 0.76 MPa, a water content of about 32% by weight, a relative ionpermeability of about 6 (relative to Alsacon lens), a contact angle offrom about 34 to 47 degrees, a WBUT of longer than 10 seconds. Whenobserved under dark field microscope, no cracking lines are visibleafter rubbing the test lens. The lenses are very lubricious in a fingerrubbing test and equivalent to the control lenses.

Example 21

SiHy lenses and IPC salines in lens packages after autoclave, which areprepared in Examples 6, 14 and 20, are subjected to followingbiocompatibility studies.

In-vitro Cytotoxicity Evaluation. SiHy lenses are evaluated by the USPDirect Contact Material Assay. Lens extracts are evaluated by the USPMEM Elution and ISO CEN Cell Growth Inhibition Assay, and the IPC salinein the packages after autoclave is evaluated by a Modified Elution test.All lens and lens extracts evaluated are well within acceptance criteriafor each test and no unacceptable cytotoxicity is observed.In-vivo Testing. ISO Systemic Toxicity in the Mouse shows that there isno evidence of systemic toxicity in the mouse with extracts of lenses.ISO Ocular Irritation Study in the Rabbit shows that extracts of lensesare not considered irritants to the ocular tissue of the rabbit. ISOOcular Irritation Study in the Rabbit shows that the IPC saline in thepackages after autoclave is not considered an irritant to the oculartissue of the rabbit. Lenses worn in a daily disposable wear mode for 22consecutive days are nonirritating to the rabbit model, and eyes treatedwith test lenses are similar to eyes treated with the control lenses.ISO Sensitization Study (Guinea Pig Maximization Testing of PackagingSolutions) shows that the IPC saline after autoclave do not cause anydelayed dermal contact sensitization in the guinea pig. ISOSensitization Study (Guinea Pig Maximization Testing of Lens Extracts)shows that Sodium chloride and sesame oil extracts of the lenses do notcause delayed dermal contact sensitization in the guinea pig.Genotoxicity Testing. When IPC salines from the lens packages and SiHylens extracts are tested in Bacterial Reverse Mutation Assay (AmesTest), it is ofund that the lens extracts and IPC salines are consideredto be nonmutagenic to Salmonella typhimurium test strains TA98, TA100,TA1535 and TA1537 and to Escherichia coli WPuvrA. When SiHy lensextracts are tested in Mammalian Erythrocyte Micronucleus Assay, theyhave no clastogenic activity and to be negative in the mouse bone marrowmicronucleus test. When IPC salines from the lens packages are testedaccording to Chromosome Aberration Test in Chinese Hamster Ovary, theIPC salines are negative for the induction of structural and numericalchromosome aberrations assays using CHO cells in both non-activated andS9-activated test systems. When SiHy lens extracts are tested accordingto Cell Gene Mutation Test (Mouse Lymphoma Mutagenesis Assay), the lensextracts are shown to be negative in the Mouse Lymphoma MutagenesisAssay.

Example 22

The surface compositions of preformed SiHy contact lenses (i.e., SiHycontact lens without any coating and prior to applying the PAA basecoating), SiHy contact lenses with PAA coating (i.e., those lensesbefore being sealed and autoclaved in lens packages with the IPCsaline), and SiHy contact lenses with a crosslinked coating thereon, allof which are prepared according to the procedures described in Example20, are determined by characterizing vacuum dried contact lenses withX-ray photoelectron spectroscopy (XPS). XPS is a method for measuringthe surface composition of lenses with a sampling depth of about 10 nm.The surface compositions of three types of lenses are reported in Table7.

TABLE 7 Surface Atomic Composition (%) SiHy Lens C N O F* Si Preformed(without coating) 58.0 6.2 23.0 0.8 12.1 With PAA coating 48.9 1.6 42.12.9 4.5 With crosslinked coating 59.1 10.8 25.4 3.2 1.4 *Fluorine isdetected, mostly likely from surface contamination during vacuum dryingprocess XPS analysis

Table 7 shows that when a PAA coating is applied onto a SiHy lens(preformed without coating), the carbon and oxygen atomic composition isclose to those of PAA (60% C and 40% O) and the silicon atomiccomposition is substantially reduced (from 12.1% to 4.5%). When acrosslinked coating is further applied onto the PAA coating, the surfacecomposition is predominated by carbon, nitrogen and oxygen, which arethe three atomic composition (excluding hydrogen because XPS does notcount hydrogen in the surface composition). Such results indicate thatthe outmost layer of the SiHy contact lens with crosslinked coating islikely to be essentially consisting of the hydrophilic polymericmaterial which is the reaction product of poly(AAm-co-AA)(90/10) (60% C,22% 0 and 18% N) and PAE.

The following commercial SiHy lenses which are vacuum-dried are alsosubjected to XPS analysis. The surface compositions of those commercialSiHy contact lenses are reported in Table 8.

TABLE 8 Surface Atomic composition (%) C N O F* Si N&DO ® Aqua ™ 68.49.1 18.6 1.5 2.4 Air Optix ® Aqua ™ 67.7 9.9 18.2 1.9 2.4 PureVision ®58.2 6.9 26.0 1.1 7.9 Premio ™ 61.1 6.9 23.6 1.8 6.6 Acuvue ® Advance ®61.1 4.9 24.9 0.7 8.4 Acuvue ® Oasys ® 61.5 5.0 24.4 0.6 8.5 TruEye ™63.2 4.9 24.2 0.8 7.0 Biofinity ® 46.5 1.4 28.9 5.3 17.9 Avaira  ™ 52.42.5 27.8 4.2 13.1 *Fluorine is detected aslo in Advance, Oasys andTrueye lenses, mostly likely from surface contamination during vacuumdrying process XPS analysis

It is found that a SiHy contact lens of the invention has a nominalsilicone content, about 1.4%, in the surface layer, much lower thanthose of commercial SiHy lenses without plasma coatings (Acuvue®Advance®, Acuvue® Oasys®, TruEye™, Biofinity®, Avaira™) and PureVision®(with plasma oxidation) and Premio™ (with unknown plasma treatment), andeven lower than the SiHy lenses with a plasma-deposited coating having athickness of about 25 nm (N&D® Aqua™ and Air Optix® Aqua™). This verylow value of Si % is comparable to the silicone atomic percentage of acontrol sample, polyethylene from Goodfellow (LDPE, d=0.015 mm; LS356526SDS; ET31111512; 3004622910). Those results indicate that the very lowvalue in the XPS analysis of vacuum dried SiHy contact lens of theinvention may be due to contaminants introduced during preparationprocessess including vacuum drying process and XPS analysis, like thefluorine content in the lenses that do not contain fluorine. Siliconehas been successfully shielded from exposure in the SiHy contact lensesof the invention.

XPS analysis of SiHy contact lenses of the invention (prepared accordingto the procedures described in Example 20), commercial SiHy contactlenses (CLARITI™ 1 Day, ACUVUE® TruEye™ (narafilcon A and narafilconB)), polyethylene sheets from Goodfellow (LDPE, d=0.015 mm; LS356526SDS; ET31111512; 3004622910), DAILIES® (polyvinylalcohol hydrogellenses, i.e., non-silicone hydrogel lenses), ACUVUE® Moist(polyhydroxyethylmethacrylate hydrogel lenses, i.e., non-siliconehydrogel lenses) is also carried out. All lenses are vacuum-dried.Polyethylene sheets, DAILIES® and ACUVUE® Moist are used as controlbecause they do not contain silicone. The silicone atomic compositionsin the surface layers of the test samples are as following: 1.3±0.2(polyethylene sheet); 1.7±0.9 (DAILIES®; 2.8±0.9 (ACUVUE® Moist);3.7±1.2 (three SiHy lenses prepared according to the proceduresdescribed in Example 20); 5.8±1.5 (CLARITI™ 1 Day); 7.8±0.1 (ACUVUE®TruEye™ (narafilcon A)); and 6.5±0.1 (ACUVUE® TruEye™ (narafilcon B)).The results for SiHy contact lens of the invention are closer to thoseof the traditional hydrogels then to the silicone hydrogels.

Example 23 Synthesis of UV-Absorbing Amphiphilic Branched Copolymer

A 1-L jacketed reactor is equipped with 500-mL addition funnel, overheadstirring, reflux condenser with nitrogen/vacuum inlet adapter,thermometer, and sampling adapter. 89.95 g of 80% partiallyethylenically functionalized polysiloxane prepared in Example 17, A, ischarged to the reactor and then degassed under vacuum less than 1 mbarat room temperature for about 30 minutes. The monomer solution preparedby mixing 1.03 g of HEMA, 50.73 g of DMA, 2.76 g of Norblocmethacrylate, 52.07 g of TRIS, and 526.05 g of ethyl acetate is chargedto the 500-mL addition funnel followed with a degas under vacuum 100mbar at room temperature for 10 minutes and then refilled with nitrogengas. The monomer solution is degassed with same conditions foradditional two cycles. The monomer solution is then charged to thereactor. The reaction mixture is heated to 67° C. with adequatestirring. While heating, a solution composed of 2.96 g ofmercaptoethanol (chain transfer agent, CTA) and 0.72 g of dimethyl2,2′-azobis(2-methylpropionate) (V-601-initiator) and 76.90 g of ethylacetate is charged to the addition funnel followed by same degas processas the monomer solution. When the reactor temperature reaches 67° C.,the initiator/CTA solution is also added to reactor. The reaction isperformed at 67° C. for 8 hours. After the copolymerization iscompleted, reactor temperature is cooled to room temperature.

Synthesis of UV-Absorbing Amphiphilic Branched Prepolymer

The copolymer solution prepared above is ethylenically functionalized toform an amphiphilic branched prepolymer by adding 8.44 g of IEM (or2-isocyanatoethyl methacrylate in a desired molar equivalent amount) inthe presence of 0.50 g of DBTDL. The mixture is stirred at roomtemperature under a sealed condition for 24 hours. The preparedprepolymer is then stabilized with 100 ppm of hydroxy-tetramethylenepiperonyloxy before the solution is concentrated to 200 g (˜50%) andfiltered through 1 um pore size filter paper. After the reaction solventis exchanged to 1-propanol through repeated cycles of evaporation anddilution, the solution is ready to be used for formulation. The solidcontent is measured via removing the solvent at vacuum oven at 80° C.

Preparation of Lens Formulation

A lens formulation is prepared to have the following composition: 71% byweight of prepolymer prepared above; 4% by weight of DMA; 1% by weightof TPO; 1% by weight of DMPC; 1% by weight of Brij 52 (from), and 22% byweight of 1-PrOH.

Lens Preparation

Lenses are fabricated by cast-molding of the lens formulation preparedabove using reusable mold, similar to the mold shown in FIGS. 1-6 inU.S. Pat. Nos. 7,384,590 and 7,387,759 (FIGS. 1-6) under spatiallimitation of UV irradiation. The mold comprises a female mold half madeof glass and a male mold half made of quartz. The UV irradiation sourceis a Hamamatsu lamp with a 380 nm-cut-off filter at an intensity ofabout 4.6 mW/cm². The lens formulation in the mold is irradiated with UVirradiation for about 30 seconds.

Cast-molded lenses are extracted with methyl ethyl ketone (MEK), rinsedin water, coated with polyacrylic acid (PAA) by dipping lenses in apropanol solution of PAA (0.004% by weight, acidified with formic acidto about pH 2.0), and hydrated in water.

IPC Saline is prepared from a composition containing about 0.07%PAAm-PAA and sufficient PAE to provide an initial azetidinium content ofapproximately 8.8 millimole equivalents/Liter (˜0.15% PAE) underpre-reaction conditions of 6 hrs at approximately 60° C. 5 ppm hydrogenperoxide is then added to the IPC salines to prevent bioburden growthand the IPC salines are filtered using a 0.22 micron polyether sulphone[PES] membrane filter Lenses are placed in a polypropylene lenspackaging shell with 0.6 mL of the IPC saline (half of the saline isadded prior to inserting the lens). The blister is then sealed with foiland autoclaved for 30 min at 121° C.

Lens Characterization

The obtained lenses have the following properties: E′˜0.82 MPa;DK_(c)˜159.4 (using lotrafilcon B as reference lenses, an average centerthickness of 80 μm and an intrinsic Dk 110); IP˜2.3; water %-26.9; andUVA/UVB % T˜4.6/0.1. When observed under dark field microscope, nocracking lines are visible after rubbing the test lens. The lenses arevery lubricious in a finger rubbing test and equivalent to the controllenses.

Example 24 Preparation of Lens Formulations

Formulation I is prepared by dissolving components in 1-propanol to havethe following composition: 33% by weight of CE-PDMS macromer prepared inExample 2, 17% by weight ofN-[tris(trimethylsiloxy)-silylpropyl]acrylamide (TRIS-Am), 24% by weightof N,N-dimethylacrylamide (DMA), 0.5% by weight ofN-(carbonyl-methoxypolyethyleneglycol-2000)-1,2-disteaoyl-sn-glycero-3-phosphoethanolamin, sodium salt)(L-PEG), 1.0% by weight Darocur 1173 (DC1173), 0.1% by weight ofvisitint (5% copper phthalocyanine blue pigment dispersion intris(trimethylsiloxy)silylpropylmethacrylate, TRIS), and 24.5% by weightof 1-propanol.

Formulation II is prepared by dissolving components in 1-propanol tohave the following composition: about 32% by weight of CE-PDMS macromerprepared in Example 2, about 21% by weight of TRIS-Am, about 23% byweight of DMA, about 0.6% by weight of L-PEG, about 1% by weight ofDC1173, about 0.1% by weight of visitint (5% copper phthalocyanine bluepigment dispersion in TRIS), about 0.8% by weight of DMPC, about 200 ppmH-tempo, and about 22% by weight of 1-propanol.

Preparation of Lenses

Lenses are prepared by cast-molding from a lens formulation preparedabove in a reusable mold (quartz female mold half and glass male moldhalf), similar to the mold shown in FIGS. 1-6 in U.S. Pat. Nos.7,384,590 and 7,387,759 (FIGS. 1-6). The UV irradiation source is aHamamatsu lamp with the WG335+TM297 cut off filter at an intensity ofabout 4 mW/cm². The lens formulation in the mold is irradiated with UVirradition for about 25 seconds. Cast-molded lenses are extracted withmethyl ethyl ketone (MEK) (or propanol or isopropanol).

Application of PAA Prime Coating onto SiHy Contact Lenses

A polyacrylic acid coating solution (PAA-1) is prepared by dissolving anamount of PAA (M.W.: 450 kDa, from Lubrizol) in a given volume of1-propanol to have a concentration of about 0.39% by weight and the pHis adjusted with formic acid to about 2.0.

Another PAA coating solution (PAA-2) is prepared by dissolving an amountof PAA (M.W.: 450 kDa, from Lubrizol) in a given volume of anorganic-based solvent (50/50 1-propanol/H₂O) to have a concentration ofabout 0.39% by weight and the pH is adjusted with formic acid to about2.0.

Above-obtained SiHy contact lenses are subjected to one of dippingprocesses shown in Tables 9 and 10.

TABLE 9 Dipping Process Baths Time 20-0 20-1 20-2 20-3 20-4 20-5 1 56 sH2O H2O H2O H2O H2O H2O 2 44 s MEK MEK MEK MEK MEK MEK 3 56 s MEK MEKMEK MEK MEK MEK 4 56 s MEK MEK MEK MEK MEK MEK 5 56 s MEK MEK MEK MEKMEK MEK 6 56 s MEK MEK MEK MEK MEK MEK 7 56 s MEK MEK MEK MEK MEK MEK 856 s H2O H2O H2O H2O H2O H2O 9 44 s PAA-1 PAA-1 PAA-1 PAA-2 PAA-2 PAA-110 56 s PAA-1 PAA-1 PAA-1 PAA-2 PAA-2 PAA-1 11 56 s H2O PrOH H2O H2O H2OH2O 12 44 s H2O PrOH PrOH PrOH 50/50 50/50 13 56 s H2O H2O H2O H2O H2OH2O 14 56 s H2O H2O H2O H2O H2O H2O 15 56 s PBS PBS PBS PBS PBS PBS 1656 s H2O H2O H2O H2O H2O H2O PrOH represents 100% 1-propanol; PBS standsfor phosphate-buffered saline; MEK stands for methyl ethyl keton; 50/50stands a solvent mixture of 50/50 1-PrOH/H₂O.

TABLE 10 Dipping Process Baths Time 80-0 80-1 80-2 80-3 80-4 80-5 80-6 156 s H2O H2O H2O H2O H2O H2O H2O 2 44 s MEK MEK MEK MEK MEK MEK MEK 3 56s MEK MEK MEK MEK MEK MEK MEK 4 56 s MEK MEK MEK MEK MEK MEK MEK 5 56 sMEK MEK MEK MEK MEK MEK MEK 6 56 s MEK MEK MEK MEK MEK MEK MEK 7 56 sMEK MEK MEK MEK MEK MEK MEK 8 56 s H2O H2O H2O H2O H2O H2O H2O 9 44 sPAA-1 PAA-1 PAA-1 PAA-1 PAA- PAA- PAA- 1 1 1 10 56 s PAA-1 50/50 PrOH50/50 PrOH PrOH H2O 11 56 s H2O H2O H2O 50/50 PrOH 50/50 50/50 12 44 sH2O H2O H2O H2O H2O H2O H2O 13 56 s H2O H2O H2O H2O H2O H2O H2O 14 56 sH2O H2O H2O H2O H2O H2O H2O 15 56 s PBS PBS PBS PBS PBS PBS PBS 16 56 sH2O H2O H2O H2O H2O H2O H2O PrOH represents 100% 1-propanol; PBS standsfor phosphate-buffered saline; MEK stands for methyl ethyl keton; 50/50stands a solvent mixture of 50/50 1-PrOH/H₂O.

Application of Crosslinked Hydrophilic Coating

Poly(acrylamide-co-acrylic acid) partial sodium salt,Poly(AAm-co-AA)(90/10) (˜90% solid content, poly(AAm-co-AA) 90/10, Mw200,000) is purchased from Polysciences, Inc. and used as received. PAE(Kymene, an azetidinium content of 0.46 assayed with NMR) is purchasedfrom Ashland as an aqueous solution and used as received. Anin-package-crosslinking (IPC) saline is prepared by dissolving about0.07% w/w of poly(AAm-co-AA)(90/10) and about 0.15% of PAE (an initialazetidinium millimolar equivalents of about 8.8 millimole) in phosphatebuffered saline (PBS) (about 0.044 w/w % NaH₂PO₄.H₂O, about 0.388 w/w/%Na₂HPO₄.2H₂O, about 0.79 w/w % NaCl) and adjusting the pH to 7.2˜7.4.Then the IPC saline is heat pre-treated for about 4 hours at about 70°C. (heat pretreatment). During this heat pretreatment, poly(AAm-co-AA)and PAE are partially crosslinked to each other (i.e., not consuming allazetidinium groups of PAE) to form a water-soluble andthermally-crosslinkable hydrophilic polymeric material containingazetidinium groups within the branched polymer network in the IPCsaline. After the heat pre-treatment, the IPC saline is filtered using a0.22 micron polyether sulphone [PES] membrane filter and cooled downback to room temperature. 10 ppm hydrogen peroxide is then added to thefinal IPC saline to prevent bioburden growth and the IPC saline isfiltered using a 0.22 micron polyether sulphone [PES]membrane filter.

Lenses having a PAA prime coating thereon prepared above are placed inpolypropylene lens packaging shells (one lens per shell) with 0.6 mL ofthe IPC saline (half of the saline is added prior to inserting thelens). The blisters are then sealed with foil and autoclaved for about30 minutes at about 121° C., forming SiHy contact lenses withcrosslinked hydrophilic coatings thereon.

Characterization of SiHy Lenses.

The resultant SiHy contact lenses with crosslinked hydrophilic coatingsthereon and a center thickness of about 0.95 microns have an oxygenpermeability (Dk_(c) or estimated intrinsic Dk) of about 142 to about150 barrers, a bulk elastic modulus of about 0.72 to about 0.79 MPa, awater content of about 30% to about 33% by weight, a relative ionpermeability of about 6 (relative to Alsacon lens), and a contact angleof from about 34 to about 47 degrees.

Characterization of the Nano-Textured Surfaces of Contact Lens

Transmission-Differential-Interference-Contrast (TDIC) Method. Contactlenses are placed on a glass slide and flattened by compressing the lensbetween the slide and a glass cover slip. Contact lens surfaces arelocated and examined by focusing through the lens using a Nikon ME600microscope with transmission differential interference contrast opticsusing a 40× objective lens. The obtained TDIC images are then evaluatedto determine the presence of winkled surface patterns (e.g., randomand/or ordered worm-like patterns, or the likes).

Reflection-Differential-Interference-Contrast (RDIC) Method. Lenses areplaced on a glass slide and flattened by making 4 radial cuts every ˜90degrees. Excess saline is blown off the surface using compressed air.Lens surface is then examined using Nikon Optiphot-2 with reflectiondifferential interference contrast optics for the presence of winkledsurface patterns on the surfaces of a contact lens using 10×, 20× and50× objective lenses. A representative image of each side is acquiredusing 50× objective lens. The contact lens is then flipped over, excesssaline removed and the other side of the contact lens and is inspectedin the same way. The obtained RDIC images are then evaluated todetermine the presence of winkled surface patterns (e.g., random and/orordered worm-like patterns, or the likes).

Dark Field Light Microscopy (DFLM). DFLM is generally based on darkfield illumination which is a method of enhancing contrast in observedsamples. This technique consists of a light source outside or blockedfrom the observer's field of view in order to illuminate a sample at anangle relative to normal transmitted light. Since the un-scattered lightfrom the source is not gathered by the objective lens, it is not part ofthe image and the background of the image appears dark. Since the lightsource is illuminating the sample at an angle, the light observed in thesample image is that which is scatted by the sample toward the observer,contrast is then created between this scattered light from the sampleand the dark background of the image. This contrast mechanism makes darkillumination especially useful for the observation of scatteredphenomena such as haze.

DFLM is used to evaluate the haziness of contact lenses as follows. Itis believed that since the dark-field setup involves scattered light,dark-field data could provide the worst-case estimate of haziness. In8-bit grey scale digital images each image pixel is assigned a greyscale intensity (GSI) value in the range from 0-255. Zero represents apixel that is perfectly black and 255 represents a pixel that isperfectly white. An increase in the scattered light captured in theimage will produce pixels with higher GSI values. This GSI value canthen be used as a mechanism to quantify the amount of scattered lightobserved in a dark field image. The haziness is expressed by averagingthe GSI values of all pixels in an area of interest (AOI) (e.g., a wholelens or the lenticular zone or optical zone of a lens). The experimentalset-up consists of a microscope or equivalent optics, an attacheddigital camera and a dark field stand with ring light and variableintensity light source. Optics is designed/arranged so that the entiretyof the contact lens to be observed fills the field of view (typically˜15 mm×20 mm field of view). Illumination is set to a level appropriateto observe the desired changes in the relevant samples. Light intensityis adjusted/calibrated to the same level for each set of samples using adensity/light scattering standard as known to a person skilled in theart. For example, a standard is composed of two overlapping plasticcover slips (identical and slight or moderately frosted). Such standardconsists of areas with three different averaged GSI that include twoareas with intermediate grey scale levels and saturated white (edges).The black areas represent the empty dark field. The black and saturatedwhite areas can be used to verify gain and offset (contrast andbrightness) settings of camera. The intermediate grey levels can providethree points to verify the linear response of the camera. Lightintensity is adjusted so that the average GSI of the empty dark fieldapproaches 0 and that of a defined A01 in a digital image of thestandard is the same each time within ±5 GSI units. After lightintensity calibration, a contact lens is immersed in 0.2 μm-filteredphosphate buffer saline in a quartz Petri dish or a dish or similarclarity which is placed on the DFLM stand. An 8-bit grey scale digitalimage of the lens is then acquired as viewed using the calibratedillumination and the average GSI of a defined A01 within the portion ofthe image containing the lens is determined. This is repeated for asample set of contact lenses. Light intensity calibration isre-evaluated periodically over the course of a test to ensureconsistency. The level of haziness under DFLM examination refers to aDFLM haziness GSI/255×100%.

SiHy contact lenses, the PAA prime coating of which is obtainedaccording to either of the dipping processes 20-0 and 80-0, aredetermined to have an averaged DFLM haziness of about 73% and showwrinkle surface patterns (random worm-like patterns) that can bevisually observed by examining the contact lens in hydrated state,according to the method of either RDIC or TDIC as described above. But,the winkled surface patterns have practically no adverse effects uponthe light transmissibility of the contact lenses.

SiHy contact lenses, the PAA prime coating of which is obtainedaccording to either of the dipping processes 20-1 to 20-4, aredetermined to have a low averaged DFLM haziness of about 26% (probablydue to the presence of visitint pigment particles) and show nonoticeable wrinkle surface patterns (random worm-like patterns) whenexamined under either RDIC or TDIC as described above.

A high percentage of SiHy contact lenses, the PAA prime coating of whichis obtained according to either of the dipping process 20-5, aredetermined to have a moderate averaged DFLM haziness of about 45% andshow slightly noticeable wrinkle surface patterns when examined undereither RDIC or TDIC as described above. But, the winkled surfacepatterns have practically no adverse effects upon the lighttransmissibility of the contact lenses.

SiHy contact lenses, the PAA prime coating of which is obtainedaccording to either of the dipping processes 80-1, 80-2, 80-3, 80-5 and80-6, do not show noticeable wrinkle surface patterns when examinedunder either RDIC or TDIC as described above. But, SiHy contact lenses,the PAA prime coating of which is obtained according to either of thedipping processes 80-0 and 80-4, show noticeable wrinkle surfacepatterns when examined under either RDIC or TDIC as described above.But, the winkled surface patterns have practically no adverse effectsupon the light transmissibility of the contact lenses.

1. A method for producing silicone hydrogel contact lenses withcrosslinked hydrophilic coatings thereon, comprising the steps of: (a)obtaining a silicone hydrogel contact lens having amino groups and/orcarboxyl groups on and/or near its surface and a water-soluble andthermally-crosslinkable hydrophilic polymeric material, wherein thesilicone hydrogel contact lens comprises amino groups or carboxyl groupsor both on and/or near the surface of the contact lens, wherein thehydrophilic polymeric material comprises (i) from about 20% to about 95%by weight of first polymer chains derived from anepichlorohydrin-functionalized polyamine or polyamidoamine, (ii) fromabout 5% to about 80% by weight of hydrophilic moieties or secondpolymer chains derived from at least one hydrophilicity-enhancing agenthaving at least one reactive functional group selected from the groupconsisting of amino group, carboxyl group, thiol group, and combinationthereof, and (iii) positively-charged azetidinium groups which are partsof the first polymer chains or pendant or terminal groups covalentlyattached to the first polymer chains, wherein the hydrophilic moietiesor second polymer chains are covalently attached to the first polymerchains through one or more covalent linkages each formed between oneazetitdinium group of the epichlorohydrin-functionalized polyamine orpolyamidoamine and one amino, carboxyl or thiol group of thehydrophilicity-enhancing agent; and (b) heating the silicone hydrogelcontact lens in an aqueous solution in the presence of the hydrophilicpolymeric material to and at a temperature from about 40° C. to about140° C. for a period of time sufficient to covalently attach thehydrophilic polymeric material onto the surface of the silicone hydrogelcontact lens through second covalent linkages each formed between oneazetidinium group of the hydrophilic polymeric material and one of thereactive functional groups on and/or near the surface of the contactlens, thereby forming a crosslinked hydrophilic coating on the siliconehydrogel contact lens, wherein the silicone hydrogel contact lens withthe crosslinked hydrophilic coating thereon has a surface wettabilitycharacterized by having an averaged water contact angle of about 90degrees or less.
 2. The method of claim 1, wherein thehydrophilicity-enhancing agent is a hydrophilic polymers having one ormore amino, carboxyl and/or thiol groups, wherein the content ofmonomeric units having an amino, carboxyl or thiol group in thehydrophilic polymer as the hydrophilicity-enhancing agent is less thanabout 40% by weight based on the total weight of the hydrophilicpolymer.
 3. The method of claim 2, wherein the hydrophilic polymer asthe hydrophilicity-enhancing agent is: a polyethylene glycol having onesole amino, carboxyl or thiol group; a polyethylene glycol with twoterminal amino, carboxyl and/or thiol groups; multi-arm polyethyleneglycol with one or more amino, carboxyl and/or thiol groups;polyethylene glycol dendrimers with one or more amino, carboxyl and/orthiol groups.
 4. The method of claim 2, wherein the hydrophilic polymeras the hydrophilicity-enhancing agent is a copolymer which is apolymerization product of a composition comprising (1) about 60% byweight or less by weight of at least one reactive vinylic monomer and(2) at least one non-reactive hydrophilic vinylic monomer and/or atleast one phosphorylcholine-containing vinylic monomer; or combinationsthereof; wherein the reactive vinylic monomer is selected from the groupconsisting of amino-C₁-C₆ alkyl(meth)acrylate, C₁-C₆ alkylamino-C₁-C₆alkyl(meth)acrylate, allylamine, vinylamine, amino-C₁-C₆alkyl(meth)acrylamide, C₁-C₆ alkylamino-C₁-C₆ alkyl (meth)acrylamide,acrylic acid, C₁-C₁₂ alkylacrylic acid, N,N-2-acrylamidoglycolic acid,beta-methyl-acrylic acid, alpha-phenyl acrylic acid, beta-acryloxypropionic acid, sorbic acid, angelic acid, cinnamic acid,1-carobxy-4-phenyl butadiene-1,3, itaconic acid, citraconic acid,mesaconic acid, glutaconic acid, aconitic acid, maleic acid, fumaricacid, tricarboxy ethylene, and combinations thereof; wherein thenon-reactive hydrophilic vinylic monomer is selected from the groupconsisting of acrylamide, methacrylamide, N,N-dimethylacrylamide,N,N-dimethylmethacrylamide, N-vinylpyrrolidone,N,N,-dimethylaminoethylmethacrylate, N,N-dimethylaminoethylacrylate,N,N-dimethylaminopropylmethacrylamide,N,N-dimethylaminopropylacrylamide, glycerol methacrylate,3-acryloylamino-1-propanol, N-hydroxyethyl acrylamide,N-[tris(hydroxymethyl)methyl]-acrylamide,N-methyl-3-methylene-2-pyrrolidone, 1-ethyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 1-ethyl-5-methylene-2-pyrrolidone,5-methyl-3-methylene-2-pyrrolidone, 5-ethyl-3-methylene-2-pyrrolidone,2-hydroxyethyl(meth)acrylate, hydroxypropyl (meth)acrylate, C₁-C₄-alkoxypolyethylene glycol (meth)acrylate having a weight average molecularweight of up to 1500 Daltons, N-vinyl formamide, N-vinyl acetamide,N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, allyl alcohol, vinylalcohol (hydrolyzed form of vinyl acetate in the copolymer), andcombinations thereof.
 5. The method of claim 2, wherein the hydrophilicpolymer as the hydrophilicity-enhancing agent is a monoamino-,monocarboxyl-, diamino- or dicarboxyl-terminated homo- or copolymer of anon-reactive hydrophilic vinylic monomer selected from the groupconsisting of acryamide, N,N-dimethylacrylamide, N-vinylpyrrolidone,N-vinyl-N-methyl acetamide, glycerol (meth)acrylate,hydroxyethyl(meth)acrylate, N-hydroxyethyl (meth)acrylamide,(meth)acryloyloxyethyl phosphorylcholine, C₁-C₄-alkoxy polyethyleneglycol (meth)acrylate having a weight average molecular weight of up to400 Daltons, vinyl alcohol, N-methyl-3-methylene-2-pyrrolidone,1-methyl-5-methylene-2-pyrrolidone, 5-methyl-3-methylene-2-pyrrolidone,N,N-dimethylaminoethyl(meth)acrylate, N,N-dimethylaminopropyl(metha)crylamide, and combination thereof.
 6. The method of claim 2,wherein the hydrophilic polymer as the hydrophilicity-enhancing agent isan amino- or carboxyl-containing polysaccharide, hyaluronic acid,chondroitin sulfate, and combinations thereof.
 7. The method of claim 2,wherein the weight average molecular weight M_(w) of the hydrophilicpolymer as the hydrophilicity-enhancing agent is from about 500 to about1,000,000.
 8. The method of claim 2, wherein thehydrophilicity-enhancing agent is: amino-, carboxyl- or thiol-containingmonosaccharides; amino-, carboxyl- or thiol-containing disaccharides;and amino-, carboxyl- or thiol-containing oligosaccharides.
 9. Themethod of claim 2, wherein the step of heating is performed byautoclaving the silicone hydrogel contact lens immersed in a packagingsolution in a sealed lens package at a temperature of from about 118° C.to about 125° C. for approximately 20-90 minutes to form the crosslinkedhydrophilic coating on the silicone hydrogel contact lens, wherein thepackaging solution comprises at least one buffering agent in an amountsufficient to maintain a pH of from about 6.0 to about 8.5 and has atonicity of from about 200 to about 450 milliosmol (mOsm) and aviscosity of from about 1 centipoise to about 20 centipoises at 25° C.10. The method of claim 9, wherein the packaging solution comprises fromabout 0.01% to about 2% by weight of the thermally-crosslinkablehydrophilic polymeric material.
 11. The method of claim 9, wherein themethod further comprises: before the step of heating, contacting at roomtemperature the silicone hydrogel contact lens with an aqueous solutionof the thermally-crosslinkable hydrophilic polymeric material to form atop layer of the thermally-crosslinkable hydrophilic polymeric materialon the surface of the silicone hydrogel contact lens, immersing thesilicone hydrogel contact lens with the top layer of thethermally-crosslinkable hydrophilic polymeric material in the packagingsolution in the lens package; and sealing the lens package.
 12. Themethod of claim 9, wherein the silicone hydrogel contact lens is made bypolymerizing a silicone hydrogel lens formulation comprising from about0.1% to about 10% by weight of a reactive vinylic monomer selected fromthe group consisting of amino-C₂-C₆ alkyl (meth)acrylate, C₁-C₆alkylamino-C₂-C₆ alkyl(meth)acrylate, allylamine, vinylamine,amino-C₂-C₆ alkyl(meth)acrylamide, C₁-C₆ alkylamino-C₂-C₆alkyl(meth)acrylamide, acrylic acid, C₁-C₁₂ alkylacrylic acid,N,N-2-acrylamidoglycolic acid, beta methyl-acrylic acid, alpha-phenylacrylic acid, beta-acryloxy propionic acid, sorbic acid, angelic acid,cinnamic acid, 1-carobxy-4-phenyl butadiene-1,3, itaconic acid,citraconic acid, mesaconic acid, glutaconic acid, aconitic acid, maleicacid, fumaric acid, tricarboxy ethylene, and combinations thereof. 13.The method of claim 12, wherein the silicone hydrogel contact lenscomprises a reactive base coating including amino and/or carboxylgroups.
 14. The method of claim 13, wherein the reactive base coatingcomprises at least one layer of a reactive polymer having pendant aminogroups and/or carboxyl groups and is obtained by contacting the siliconehydrogel contact lens with a solution of the reactive polymer, whereinthe reactive polymer is: a homopolymer of amino-C₁ to C₄alkyl(meth)acrylamide, amino-C₁ to C₄ alkyl(meth)acrylate, C₁ to C₄alkylamino-C₁ to C₄ alkyl(meth)acrylamide, C₁ to C₄ alkylamino-C₁ to C₄alkyl(meth)acrylate, allylamine, or vinylamine; polyethyleneimine; apolyvinylalcohol with pendant amino groups; a linear or branchedpolyacrylic acid; a homopolymer of C₁ to C₁₂ alkylacrylic acid; acopolymer of amino-C₂ to C₄ alkyl(meth)acrylamide, amino-C₂ to C₄alkyl(meth)acrylate, C₁ to C₄ alkylamino-C₂ to C₄ alkyl(meth)acrylamide,C₁ to C₄ alkylamino-C₂ to C₄ alkyl(meth)acrylate, acrylic acid, C₁ toC₁₂ alkylacrylic acid, maleic acid, and/or fumaric acid, with at leastone non-reactive hydrophilic vinylic monomer; a carboxyl-containingcellulose; hyaluronate; chondroitin sulfate; poly(glutamic acid);poly(aspartic acid); or combinations thereof.
 15. The method of claim13, wherein the reactive polymer for forming a base coating ispolyacrylic acid, polymethacrylic acid, poly(C₂-C₁₂ alkylacrylic acid),poly[acrylic acid-co-methacrylic acid], poly[C₂-C₁₂ alkylacrylicacid-co-(meth)acrylic acid], poly(N,N-2-acrylamidoglycolic acid),poly[(meth)acrylic acid-co-acrylamide], poly[(meth)acrylicacid-co-vinylpyrrolidone], poly[C₂-C₁₂ alkylacrylic acid-co-acrylamide],poly[C₂-C₁₂ alkylacrylic acid-co-vinylpyrrolidone], hydrolyzedpoly[(meth)acrylic acid-co-vinylacetate], hydrolyzed poly[C₂-C₁₂alkylacrylic acid-co-vinylacetate], polyethyleneimine (PEI),polyallylamine hydrochloride (PAH) homo- or copolymer, polyvinylaminehomo- or copolymer, or combinations thereof.
 16. The method of claim 15,wherein the reactive polymer is dissolved in a mixture of water and oneor more organic solvents, an organic solvent, or a mixture of one ormore organic solvents.
 17. The method of claim 13, wherein the reactivebase coating on the contact lens is obtained by polymerizing at leastone amino-containing or carboxyl-containing vinylic monomer under theeffect of a plasma.
 18. A silicone hydrogel contact lens productobtained according to a method of claim 16, wherein the siliconehydrogel contact lens has at least one property selected from the groupconsisting of: an oxygen permeability of at least about 40 barrers; anelastic modulus of about 1.5 MPa or less; an lonoflux DiffusionCoefficient, D, of, at least about 1.5×10⁻⁶ mm²/min; a water content ofpreferably from about 18% to about 70% by weight when fully hydrated;and combinations thereof.
 19. An ophthalmic lens product, whichcomprises a sterilized and sealed lens package, wherein the lens packagecomprises: a post-autoclave lens packaging solution and a readily-usablesilicone hydrogel contact lens immersed therein, wherein thereadily-usable silicone hydrogel contact lens comprises a crosslinkedhydrophilic coating obtained by autoclaving an original siliconehydrogel contact lens having amino groups and/or carboxyl groups onand/or near the surface of the original silicone hydrogel contact lensin a pre-autoclave packaging solution containing a water-soluble andthermally-crosslinkable hydrophilic polymeric material, wherein thethermally-crosslinkable hydrophilic polymeric material comprises (i)from about 20% to about 95% by weight of first polymer chains derivedfrom an epichlorohydrin-functionalized polyamine or polyamidoamine, (ii)from about 5% to about 80% by weight of hydrophilic moieties or secondpolymer chains derived from at least one hydrophilicity-enhancing agenthaving at least one reactive functional group selected from the groupconsisting of amino group, carboxyl group, thiol group, and combinationthereof, and (iii) azetidinium groups which are parts of the firstpolymer chains or pendant or terminal groups covalently attached to thefirst polymer chains, wherein the thermally-crosslinkable hydrophilicpolymeric material is covalently attached onto the original siliconehydrogel contact lens through first covalent linkages each formedbetween one amino or carboxyl group on and/or near the surface of theoriginal silicone hydrogel contact lens and one azetidinium group of thethermally-crosslinkable hydrophilic polymeric material, wherein thepost-autoclave packaging solution comprises at least one buffering agentin an amount sufficient to maintain a pH of from about 6.0 to about 8.5and has a tonicity of from about 200 to about 450 milliosmol, and aviscosity of from about 1 centipoise to about 20 centipoises at 25° C.,wherein the post-autoclave packaging solution comprises a polymericwetting material which is an hydrolyzed product of thethermally-crosslinkable hydrophilic polymeric material after autoclave,wherein the readily-usable silicone hydrogel contact lens has a surfacehydrophilicity/wettability characterized by having an averaged watercontact angle of about 90 degrees or less.
 20. A water-soluble andthermally-crosslinkable hydrophilic polymeric material, comprising: (a)from about 20% to about 95% by weight of first polymer chains derivedfrom an epichlorohydrin-functionalized polyamine or polyamidoamine; (b)from about 5% to about 80% by weight of second polymer chains derivedfrom at least one hydrophilicity-enhancing polymeric agent having atleast one reactive functional group selected from the group consistingof amino group, carboxyl group, thiol group, and combination thereof,wherein the second polymer chains are covalently attached to the firstpolymer chains through one or more covalent linkages each formed betweenone azetitdinium group of the epichlorohydrin-functionalized polyamineor polyamidoamine and one amino, carboxyl or thiol group of thehydrophilicity-enhancing polymeric agent; and (c) azetidinium groupswhich are parts of the first polymer chains or pendant groups covalentlyattached to the first polymer chains.